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'''Obesity''' is the medical condition associated with excessive stores of body fat, to the extent that it causes serious health concerns.
'''Obesity''' is the medical condition associated with excessive stores of [[adipocyte|body fat]], to the extent that it causes serious health risks. Physical problems include [[hypertension|high blood pressure]], heart disease, some cancers and [[Diabetes mellitus type 2]];  emotional problems include low self esteem, and depression.  More than a billion people are classed as obese worldwide, and by 2025, 300 million people are expected to suffer from [[Diabesity|obesity-related diabetes]].
   
==Causes/etiology==


Obesity is caused by a mix of environmental and genetic factors.<ref name="pmid2336075">{{cite journal |author=Stunkard AJ ''et al.''|title=The body-mass index of twins who have been reared apart |journal=N. Engl. J. Med. |volume=322 |issue=21 |pages=1483–7 |year=1990 |pmid=2336075 |doi=}}</ref><ref name="pmid17652652">{{cite journal |author=Christakis NA, Fowler JH |title=The spread of obesity in a large social network over 32 years |journal=N Engl J Med |volume=357 | |pages=370–9 |year=2007 |pmid=17652652 |doi=10.1056/NEJMsa066082}}</ref>
There are many ways of measuring body fat, but the most common  measures the relationship between weight and height by the [[body mass index]] (BMI). A BMI of 30 or more puts you in the category of ''obese''.  This method is simple, but imprecise; people with well-developed muscle may have a high BMI yet a low proportion of body fat.
===Genetics===


In only very few cases can obesity in humans be attributed to a single gene defect, but many genes have been found that have variants associated with an increased risk of obesity. One of the few genes that variants in the human population associated with increased risk of obesity is the gene for the melanocortin 4 receptor (MC4R). This receptor is expressed in the [[hypothalamus]], and mediates the actions of alpha melanocyte stimulating hormone, a [[peptide]] released by a subpopulation of neurons in the [[arcuate nucleus]] in response to [[leptin]]. <ref name="pmid12646665">{{cite journal |author=Farooqi IS ''et al.''|title=Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene |journal=N Engl J Med |volume=348 |issue=12 |pages=1085–95 |year=2003 |pmid=12646665 |doi=10.1056/NEJMoa022050}}</ref> (see [[Hunger]] for more information).
==Prevalence and epidemiology==
Obesity is increasing in Europe.<ref name="pmid19286092">{{cite journal |author=Kotseva K ''et al.''|title=Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries |journal=Lancet |volume=373 |pages=929–40 |year=2009 |pmid=19286092 |url=http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(09)60330-5}}</ref> In the U.S.A., obesity is increased through 2004<ref name="pmid16595758">{{cite journal |author=Ogden CL ''et al.''|title=Prevalence of overweight and obesity in the United States, 1999-2004 |journal=JAMA |volume=295 |pages=1549–55 |year=2006 |pmid=16595758 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=16595758}}</ref> but has been stable since<ref name="pmid18505949">{{cite journal |author=Ogden CL ''et al.'' |title=High body mass index for age among US children and adolescents, 2003-2006 |journal=JAMA |volume=299  |pages=2401–5 |year=2008|pmid=18505949 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18505949}}</ref>. Among immigrants, the incidence of obesity increases with the duration of living in the U.S.A..<ref name="pmid15598917">{{cite journal |author=Goel MS ''et al.'' |title=Obesity among US immigrant subgroups by duration of residence |journal=JAMA |volume=292|pages=2860–7 |year=2004 |pmid=15598917|url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=15598917}}</ref>


===Behavioural and environmental factors===
==Causes/etiology==
 
'' See [[Genetics of obesity]]''  
The ''secular'' increase in overweight and obesity (the increase that has taken place during the XX<sup>th</sup> century and is continuing today) is most obviously due to environmental changes (in the widest sense), the most commonly discussed obesogenic factors being diet and exercise ("The Big Two"). This is not to say that no relevant obesogenic changes in the Human genetic pool happened during this period, and this does not exclude epigenetic modifications of the genome. In a multi-center review of the literature on the possible causes of this secular trend, 10 other factors, including epigenetic changes and modifications in mating behaviours modulating the gene pool, were found to be equally plausible etiologic factors contributing to the epidemic, as Keith et al. argue.<ref name="pmid16801930">{{cite journal |author=Keith SW, Redden DT, Katzmarzyk PT, ''et al'' |title=Putative contributors to the secular increase in obesity: exploring the roads less traveled |journal=Int J Obes (Lond) |volume=30 |issue=11 |pages=1585–94 |year=2006 |month=November |pmid=16801930 |url=http://www.uab.edu/images/shrp/shrp06/Putative%20contributors%20to%20the%20secular%20increase%20in%20obesity%20-%20exploring%20the%20roads%20less%20traveled.pdf}}</ref>
These factors will be discussed after a critical appraisal of the role of the Big Two.
 
====The Big Two====
 
'''Diet'''
 
'''Sedendarity'''
 
''Also see [[exercise]]''
 
While it is clear that a sedendary lifestyle is involved in the development of a wide range of physical and mental ills, and that overweight and obesity are associated with a more sedendary lifestyle, it is far from obvious that lack of exercise is a major etiological factor in the present obesity epidemic. In a 5.6 years follow-up study of 393 middle-aged healthy subjects (whites), Cambridge epidemiologists demonstrated that carrying excess weight predicted a sedentary lifestyle, but that sedendary time did not predict weight gain.<ref>U Ekelund, S Brage, H Besson, S Sharp and NJ Wareham (2008) Time spent being sedentary and weight gain in healthy adults: reverse or bidirectional causality? American Journal of Clinical Nutrition, Vol. 88, No. 3, 612-617, September</ref>
 
====Other behavioural and environmental factors====
In ''Putative contributors to the secular increase in obesity: exploring the roads less traveled'',<ref name="pmid16801930"/> an analysis published in the [http://www.nature.com/ijo/index.html International Journal of Obesity], reviewers found "evidence (in favor of the following factors was) in many cases (...) as compelling as the evidence for more commonly discussed putative explanations (diet and physical activity)":
 
'''Sleep debt'''


Vgontzas et al. report primary causes of short sleep duration in obesity as chronic emotional disturbance and various difficulties sleeping.<ref name=vgontzas2008>Vgontzas AN, Lin HM, Papaliaga M, Calhoun S, Vela-Bueno A, Chrousos GP, Bixler EO. (2008) [http://dx.doi.org/10.1038/ijo.2008.4 Short sleep duration and obesity: the role of emotional stress and sleep disturbances.] ''Int. J Obes. (Lond)'' 32:801-9. PMID 18253159.
The proximate cause of obesity is a mix of environmental and genetic factors.<ref name="pmid2336075">{{cite journal |author=Stunkard AJ ''et al.''|title=The body-mass index of twins who have been reared apart |journal=N Eng J Med |volume=322 |pages=1483–7 |year=1990 |pmid=2336075}}</ref><ref name="pmid17652652">{{cite journal |author=Christakis NA, Fowler JH |title=The spread of obesity in a large social network over 32 years |journal=N Engl J Med |volume=357 | |pages=370–9 |year=2007 |pmid=17652652}}</ref> In only very few cases can obesity in humans be attributed to a single gene defect, but many genes have been found that have (usually rare) variants associated with an increased risk of obesity.  
*'''<u>Objective and Conclusion from Free Abstract:</u>'''
:*OBJECTIVE: Many epidemiologic studies have reported that obesity is associated with short sleep duration. How the degree of obesity or other clinical characteristics of the obese individuals, such as sleep disturbances or emotional stress, define this relation is not known.
:*CONCLUSION: Self-reported short sleep duration in obese individuals may be a surrogate marker of emotional stress and subjective sleep disturbances, whose detection and management should be the focus of our preventive and therapeutic strategies for obesity. </ref>


'''Endocrine disruptors'''
Obesity is generally associated with a state of [[leptin]] resistance, that is analogous to the [[insulin resistance]] seen in [[diabetes mellitus type 2 ]]. Leptin is a [[hormone]] that is secreted into the blood from fat tissues (adipocytes); it acts on the appetite-regulating centres of the [[hypothalamus]] to suppress [[appetite]], and it is secreted at high levels in most obese individuals. However, in these obese individuals, the [[hypothalamus]] does not respond appropriately to leptin.


Endocrine disruptors are man made chemicals interfering with any possible step of hormone signalling. Exposure to low levels of estrogen mimics in the womb can cause "grotesque obesity"<ref name="pmid15959888">{{cite journal |author=Newbold RR, Padilla-Banks E, Snyder RJ, Jefferson WN |title=Developmental exposure to estrogenic compounds and obesity |journal=Birth Defects Res. Part A Clin. Mol. Teratol. |volume=73 |issue=7 |pages=478–80 |year=2005 |month=July |pmid=15959888}}. Also see the [http://www.ourstolenfuture.org/NewScience/obesity/2005/2005-0615newboldetal.html overview] from the [[Our Stolen Future]] online resource:
The role of fetal programming,<ref name="pmid11738796">{{cite journal| author=Breier BH ''et al.''| title=Fetal programming of appetite and obesity|journal=Mol Cell  Endocrinol|year= 2001|volume= 185| pages= 73-9|pmid=11738796| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=11738796}}</ref> <ref name="pmid11479129">{{cite journal| author=Vickers MH ''et al.''| title=Dysregulation of the adipoinsular axis - a mechanism for the  pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal  programming|journal=J Endocrinol|year= 2001| volume=170| pages= 323-32|pmid=11479129
*'''<u>Excerpts:</u>'''
|url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=11479129}} </ref><ref name="pmid10893326">{{cite journal| author=Vickers MH ''et al.''|title=Fetal  origins of hyperphagia, obesity, and hypertension and postnatal  amplification by hypercaloric nutrition|journal=Am J  Physiol|year=2000|volume=279|pages=E83-7|pmid=10893326
:*This study with mice provides a striking example of how exposure in the womb to an estrogen mimic, diethylstilbestrol, (DES), can lead to grotesque obesity in adulthood. The level of DES required to cause the effect is extremely low... (...) Exposure to synthetic chemicals with estrogenic properties has increased dramatically over the 20th century. One of the most widespread current exposures is to bisphenol A, used to make polycarbonate plastic and other consumer products. Experiments with mice have shown that BPA exposure in the womb causes large increases in post-pubertal weight, and that exposures to very low levels during adulthood can induce insulin resistance. The CDC estimates that 95% of Americans are exposed to bisphenol A at levels within the range of concentrations used in these animal experiments.</ref>. [[Bisphenol(A)]], and perhaps other [[polycyclic aromatic hydrocarbon]]s appears to inhibit the burning of fat by interfering with [[catecholamine]]s.<ref name="pmid16689925">{{cite journal |author=Irigaray P, Ogier V, Jacquenet S, ''et al'' |title=Benzo[a]pyrene impairs beta-adrenergic stimulation of adipose tissue lipolysis and causes weight gain in mice. A novel molecular mechanism of toxicity for a common food pollutant |journal=FEBS J. |volume=273 |issue=7 |pages=1362–72 |year=2006 |month=April |pmid=16689925}}.  
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=10893326}} </ref> perhaps operative in the higher risk of obesity in offspring of older and/or very lean women.
*'''<u>Conclusions:</u>'''
:*The weight gain occurred consistently without detectable changes in food intake. These results reveal a novel molecular mechanism of toxicity for the environmental pollutant B[a]P and introduce the notion that chronic exposure of human population to B[a]P and possibly other polycyclic aromatic hydrocarbons could have an impact on metabolic disorders, such as obesity.</ref> Exposure to [[organochlorine]]s decrease [[thyroid hormone]] concentrations, resting [[metabolic rate]], and [[fat oxidation]] in [[skeletal muscles]]<ref name="pmid12608524">{{cite journal |author=Pelletier C, Imbeault P, Tremblay A |title=Energy balance and pollution by organochlorines and polychlorinated biphenyls |journal=Obes Rev |volume=4 |issue=1 |pages=17–24 |year=2003 |month=February |pmid=12608524 |url=http://www.blackwell-synergy.com/openurl?genre=article&sid=nlm:pubmed&issn=1467-7881&date=2003&volume=4&issue=1&spage=17}}</ref>.)


'''Decreased smoking'''
===Environment and lifestyle===
The increase in overweight and obesity that has taken place during the 20<sup>th</sup> century is likely to be due to environmental changes (in the widest sense), including especially lifestyle changes that affect diet and exercise habits. While a sedentary lifestyle is involved in the development of a wide range of physical and mental ills, and obesity is associated with a more sedentary lifestyle, it is not obvious that lack of exercise is a ''major'' factor in the present obesity epidemic. In a 5.6 years follow-up study of 393 middle-aged healthy subjects, Cambridge epidemiologists demonstrated that carrying excess weight predicted a sedentary lifestyle, but that sedentary time did not predict weight gain.<ref>Ekelund U ''et al.''(2008) Time spent being sedentary and weight gain in healthy adults: reverse or bidirectional causality? ''Am J Clin Nutr'' 88:612-7</ref> Failure of sedentary time to predict weight gain might conceivably reflect insufficient sample size to reveal a significant prediction, as might greater errors in estimating sedentary time than measuring weight change.


'''Cultural changes in perceptions of overweight'''<ref name="pmid18617488">{{cite journal |author=Johnson F, Cooke L, Croker H, Wardle J |title=Changing perceptions of weight in Great Britain: comparison of two population surveys |journal=BMJ |volume=337 |issue= |pages=a494 |year=2008 |pmid=18617488 |doi= |url= |issn=}}</ref>
Many other changes in environment and lifestyle may be involved in the increasing prevalence of obesity. In one multi-center review of the literature, 10 other factors, including epigenetic changes were found to be equally plausible etiologic factors contributing to the epidemic.<ref name="pmid16801930">{{cite journal |author=Keith SW ''et al.''|title=Putative contributors to the secular increase in obesity: exploring the roads less traveled|journal=Int J Obes|volume=30|pages=1585–94|year=2006|pmid=16801930 |url=http://www.uab.edu/images/shrp/shrp06/Putative%20contributors%20to%20the%20secular%20increase%20in%20obesity%20-%20exploring%20the%20roads%20less%20traveled.pdf}}</ref><ref name="pmid19221391">{{cite journal| author=Wansink B, Payne CR| title=The joy of cooking too much: 70 years of calorie increases in classic recipes. | journal=Ann Intern Med | year= 2009 | volume= 150 | issue= 4 | pages= 291-2 | pmid=19221391 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19221391  }} </ref>
Stress and depression (and associated disruptions of sleep) can lead to obesity.<ref name="pmid19808765">{{cite journal|author=Kivimäki M ''et al.''|title=Common mental disorder and obesity: insight from four repeat measures over 19 years: prospective Whitehall II cohort study| journal=BMJ|year=2009|volume=339|pages=b3765|pmid=19808765
|url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19808765}}</ref> <ref name="pmid18253159">{{cite journal| author=Vgontzas AN ''et al.''| title=Short sleep duration and obesity: the role of emotional stress and sleep disturbances| journal=Int J Obes|year= 2008|volume=32|pages=801-9|pmid=18253159
| url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=clinical.uthscsa.edu/cite&email=badgett@uthscdsa.edu&retmode=ref&cmd=prlinks&id=18253159}}</ref><ref name="pmid16801930"/>; changes in eating patterns may contribute<ref>{{Cite journal
| doi = 10.1161/CIR.0b013e31823ac046
| issn = 0009-7322, 1524-4539
| last = Roger
| first = V. L.
| coauthors = A. S. Go, D. M. Lloyd-Jones, E. J. Benjamin, J. D. Berry, W. B. Borden, D. M. Bravata, S. Dai, E. S. Ford, C. S. Fox, H. J. Fullerton, C. Gillespie, S. M. Hailpern, J. A. Heit, V. J. Howard, B. M. Kissela, S. J. Kittner, D. T. Lackland, J. H. Lichtman, L. D. Lisabeth, D. M. Makuc, G. M. Marcus, A. Marelli, D. B. Matchar, C. S. Moy, D. Mozaffarian, M. E. Mussolino, G. Nichol, N. P. Paynter, E. Z. Soliman, P. D. Sorlie, N. Sotoodehnia, T. N. Turan, S. S. Virani, N. D. Wong, D. Woo, M. B. Turner, on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee
| title = Heart Disease and Stroke Statistics--2012 Update: A Report From the American Heart Association
| journal = Circulation
| accessdate = 2011-12-16
| date = 2011-12-15
| url = http://circ.ahajournals.org/citmgr?gca=circulationaha;CIR.0b013e31823ac046v1
}}</ref><ref name="pmid21738451">{{cite journal| author=Duffey KJ, Popkin BM| title=Energy density, portion size, and eating occasions: contributions to increased energy intake in the United States, 1977-2006. | journal=PLoS Med | year= 2011 | volume= 8 | issue= 6 | pages= e1001050 | pmid=21738451 | doi=10.1371/journal.pmed.1001050 | pmc=PMC3125292 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21738451  }} </ref><ref>{{Cite journal|volume=337|pages= a2002|last = Maruyama|first = K|coauthors = et al.| title = The joint impact on being overweight of self reported behaviours of eating quickly and eating until full : cross sectional survey |journal = BMJ|date = 2008-10-21| url = http://www.bmj.com/cgi/content/abstract/337/oct21_2/a2002}}</ref> and cultural changes in perceptions of overweight<ref name="pmid18617488">{{cite journal |author=Johnson F ''et al.'' |title=Changing perceptions of weight in Great Britain: comparison of two population surveys |journal=BMJ |volume=337|pages=a494 |year=2008 |pmid=18617488}}</ref> Smoking cessation has a well known effect to increase caloric intake.


'''Pharmaceutical iatrogenesis'''
===&nbsp;&nbsp;Evolutionary perspectives of obesity===
To fully understand the causes and prevalence of obesity, evolutionary factors may  need integration into the mix of environmental and genetic proximate causes of obesity. [[Evolutionary medicine]] suggests we get fat because of built-in encouragements to eat heartily when we have plenty to eat and to restrict energy expenditures in preparation for inevitable food shortages. It may also suggest we consider the effect of the types of food we eat compared to those evolution adapted us to eat.  We’ve only recently, on an evolutionary timescale, begun to eat readily absorbable carbohydrates in disproportionate amounts. Our hunter-gatherer ancestors had little access to such food items, with the exception of a bit of honey.  Now we have so-called refined carbohydrates readily available and much consumed. Those include granulated sugar and sucrose dissolved in soft drinks; syrups and candies; milled cereal grain flours and their host pastries, pastas and breads; and many other processed ‘high glycemic’ foods. Those foods stimulate the secretion of insulin as control for glucose homeostasis, and induce other hormonal changes that influence appetite and efficiency of energy utilization. Science writer Gary Taubes summarizes the argument:


Many modern drugs widely used today cause weight gain.
<blockquote>“There is considerable evidence that the obesity epidemic is caused by a hormonal phenomenon, specifically by the consumption of refined carbohydrates, starches and sugars, all of which prompt (sooner or later) excessive insulin secretion. Insulin is the primary regulator of fat storage. When insulin levels are elevated, fat accumulates in our body tissue; when they fall, fat is released and we use it for fuel. By stimulating insulin secretion, carbohydrates make us fat; by driving us to accumulate fat, they increase hunger and decrease the energy we expend in metabolism and physical activity. In short, obesity is caused not by overeating or sedentary behaviour, but by hormonal malfunctioning triggered by the consumption of particular types of carbohydrate-containing foods.”<ref name=taubesns08>Taubes G. (2008) The great diet delusion: It is time for nutrition researchers and health authorities to wake up to the fact that people do not get fat simply because they overeat. ''New Scientist'' 19 January 2008, page 17</ref></blockquote>
 
'''Changes in distribution of ethnicity and age'''
 
Some age and ethnic groups where obesity is more common have grown in number)
 
'''Increasing gravida age'''
 
Giving birth at an older age, which is a worlwide trend, is a risk factor for obesity in the offspring.
 
'''Intrauterine and intergenerational effects'''
 
Trends in obesity incidence may reflect (probably epigenetic) changes that occurred a generation or more before)
 
'''Reproductive fitness'''
 
High BMI leads to reproductive fitness (reproducing at a higher rate)
 
'''Assortative mating and floor effects'''
 
A tendency to search for mates with comparable phenotypes (physical appearance), coupled to a floor effect (a loss of reproductive fitness with increasing leanness), would lead, over time, in a snowball effect to epidemic proportions of overweight.
 
These explanations neither compete with each other, nor with the "Big Two", but demand more depth to the explanations coming out of interventions and researches that are focusing solely on caloric intake and expenditure (diet and exercise).  
 
Nevertheless, any consideration of the role of increased caloric intake and decreased physical energy expenditure must also take into consideration the factors causing them. Some if not many of the above ten 'additional' contributions to the obesity epidemic, plausibly operate proximately to increase caloric intake and/or reduce physical energy expenditure. Sleep debt, for example, produces endocrine/metabolic changes in the body that increase appetite, as Keith et al. point out.<ref name="pmid16801930" /> One might not find it surprising that people suffering from sleep deprivation reduce their physical energy energy expenditure because of tiredness. No need to expend much physical energy to keep warm or cool in a thermoneutral environment.  Smoking cessation has a well known effect to increase caloric intake. The role of endocrine disruptors and pharmaceuticals requires further investigation as to the mechanisms of interruption of body weight regulation. Noting greater proportions of ethnic groups that have a propensity to obesity may help explain the rising obesity prevalence but in itself does provide causal mechanisms or exclude the proximate role of the Big Two. Keith et al. make an important contribution with their study in that their findings indicate that treatment aimed at reversing the "Big Two" will require consideration of the role of a number of factors potentially underpinning them.
 
The role of fetal programming,<ref name=breier2002>Breier BH, Vickers MH, Ikenasio BA, Chan KY, Wong WP. (2001) [http://dx.doi.org/10.1016/S0303-7207(01)00634-7 Fetal programming of appetite and obesity.] ''Mol. Cell Endocrinol.'' 185:73-9. PMID 11738796.
*'''<u>Abstract:</u>''' Obesity and related metabolic disorders are prevalent health issues in modern society and are commonly attributed to lifestyle and dietary factors. However, the mechanisms by which environmental factors modulate the physiological systems that control weight regulation and the aetiology of metabolic disorders, which manifest in adult life, may have their roots before birth. The 'fetal origins' or 'fetal programming' paradigm is based on the observation that environmental changes can reset the developmental path during intrauterine development leading to obesity and cardiovascular and metabolic disorders later in life. The pathogenesis is not based on genetic defects but on altered genetic expression as a consequence of an adaptation to environmental changes during fetal development. While many endocrine systems can be affected by fetal programming recent experimental studies suggest that leptin and insulin resistance are critical endocrine defects in the pathogenesis of programming-induced obesity and metabolic disorders. However, it remains to be determined whether postnatal obesity is a consequence of programming of appetite regulation and whether hyperphagia is the main underlying cause of the increased adiposity and the development of metabolic disorders. </ref>
<ref name=vickers2001>Vickers MH, Reddy S, Ikenasio BA, Breier BH. (2001) [http://dx.doi.org/10.1677/joe.0.1700323 Dysregulation of the adipoinsular axis -- a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming.] ''J Endocrinol.'' 170:323-32. PMID 11479129.
*'''<u>Abstract:</u>''' Obesity and its related disorders are the most prevalent health problems in the Western world. Using the paradigm of fetal programming we developed a rodent model which displays the phenotype of obesity and metabolic disorders commonly observed in human populations. We apply maternal undernutrition throughout gestation, generating a nutrient-deprived intrauterine environment to induce fetal programming. Maternal undernutrition results in fetal growth retardation and in significantly decreased body weight at birth. Programmed offspring develop hyperphagia, obesity, hypertension, hyperleptinemia and hyperinsulinism during adult life and postnatal hypercaloric nutrition amplifies the metabolic abnormalities induced by fetal programming. The adipoinsular axis has been proposed as a primary candidate for linking the status of body fat mass to the function of the pancreatic beta-cells….Our data suggest that reduced substrate supply during fetal development can trigger permanent dysregulation of the adipoinsular feedback system leading to hyperleptinemia, hyperinsulinism and compensatory leptin production by pancreatic delta-cells in a further attempt to reduce insulin hypersecretion in the progression to adipogenic diabetes. </ref>
<ref name=vickers2000>Vickers MH, Breier BH, Cutfield WS, Hofman PL, Gluckman PD. (2000) [http://ajpendo.physiology.org/cgi/content/full/279/1/E83 Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition.] ''Am J Physiol Endocrinol. Metab'' 279:E83-E87. PMID 10893326.
*'''<u>Abstract:</u>''' Environmental factors and diet are generally believed to be accelerators of obesity and hypertension, but they are not the underlying cause. Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming. Using fetal undernutrition throughout pregnancy, we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease….This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology. We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia, obesity, and hypertension as a consequence of altered fetal development. </ref>
perhaps operative in the higher risk of obesity in offspring of older and/or very lean women, emerges as an intriguing result of the analysis by Keith et al.<ref name="pmid16801930" />


== Pathophysiology ==
== Pathophysiology ==
'''Appetite: a cause and an effect'''
Obesity is associated with a state of [[leptin]] resistance, analogous to the insulin resistance seen in type 2 [[diabetes]]. Leptin (from the greek'' leptos'', "thin"), being secreted by fat tissues, is high in obese individuals. Nevertheless, the [[hypothalamus]] does not respond proportionately to these concentrations. Leptin is traditionally viewed as a major satiety signal. Indeed, leptin administration suppresses appetite. However, animals who are fed amounts of food comparable to those eaten by animals submitted to the anorexigenic (appetite-suppressing) effects of leptin do not lose weight as fast as their leptin-treated counterparts. <ref name="pmid10712302">{{cite journal |author=Rafael J, Herling AW |title=Leptin effect in ob/ob mice under thermoneutral conditions depends not necessarily on central satiation |journal=Am. J. Physiol. Regul. Integr. Comp. Physiol. |volume=278 |issue=3 |pages=R790–5 |year=2000 |month=March |pmid=10712302 |url=http://ajpregu.physiology.org/cgi/content/full/278/3/R790#Top}}"Reduction of body mass in leptin-treated ob/ob mice was faster than in pair-fed ob/ob controls" (Free full text)</ref> Going a step further, Rafael and colleagues observed that the satiety effect caused by leptin itself could be a ''consequence'' of the "dramatic" increase in fat combustion (lipolysis) elicited by leptin. In other words, leptin would cut appetite because it causes weight loss (by causing fat combustion) rather than, or in addition to, the opposite (for an exploration of the range of possible appetite-independent functions of leptin, see "Perspectives", in the Discussion section of Rafael & al.<ref name="pmid10712302"/>).
A similar change occured in our understanding of ghrelin, away from hunger signalling, and towards metabolic fine-tuning of energy utilization. [[Ghrelin]] is a hormone secreted by the stomach which is often viewed as the appetite stimulant that counteracts leptin's anorexigenic effect. Again, it appears that this hormone does not act directly as an appetite stimulant, but rather modifies the way in which the body uses fat (versus carbohydrates): it increases fat storage. Concluding their study of mutants unable to secrete ghrelin (and, as a result, less "able" to gain weight when fed a high fat diet), Wortley & al. hypothesise:
<blockquote>''The ability to efficiently build fat reserves in times of nutritional abundance appears to have resulted from evolutionary pressure to protect against subsequent periods of food scarcity. The tendency to efficiently store fat in times of caloric excess appears to have become paradoxically maladaptive in settings of continuous food availability, as indicated by the present epidemic of obesity in Western societies.''<ref name="pmid15148384">{{cite journal |author=Wortley KE, Anderson KD, Garcia K, ''et al'' |title=Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue=21 |pages=8227–32 |year=2004 |month=May |pmid=15148384 |doi=10.1073/pnas.0402763101 |url=http://www.pnas.org/cgi/content/full/101/21/8227}}(Free full text)</ref></blockquote>
[[Rimonabant]], a recently developped antagonist of [[endocannabinoid receptor]]s (receptors of endogenous [[cannabis]]-like signalling), is also often thought to induce weight loss (see Treatment, below) by decreasing appetite, as it is called an [[anorectic drug]]. The weight loss, however, extends well beyond the transient decrease in appetite. Studying candy-fed animals, researchers found that rimonabant actually increased the amount of fat available for combustion after a meal, and that this increase in availability was not an indirect, compensatory, consequence of food deprivation, but a direct neuroendocrine effect in its own right.<ref name="pmid18276749">{{cite journal |author=Herling AW, Kilp S, Elvert R, Haschke G, Kramer W |title=Increased energy expenditure contributes more to the body weight-reducing effect of rimonabant than reduced food intake in candy-fed wistar rats |journal=Endocrinology |volume=149 |issue=5 |pages=2557–66 |year=2008 |month=May |pmid=18276749 |doi=10.1210/en.2007-1515 |url=http://endo.endojournals.org/cgi/content/abstract/en.2007-1515v1}} (Free full text)</ref> It is now known that blocking type 1 cannabinoid receptors triggers the birth of new mitochondria (the fat-burning power plants of the cells) in fat cells,<ref name="pmid18477809">{{cite journal |author=Tedesco L, Valerio A, Cervino C, ''et al'' |title=Cannabinoid type 1 receptor blockade promotes mitochondrial biogenesis through eNOS expression in white adipocytes |journal=Diabetes |volume= |issue= |pages= |year=2008 |month=May |pmid=18477809 |doi=10.2337/db07-1623 |url=}}</ref> obviously a beneficial effect for weight loss (also see below, end of section).
'''The response to a meal in obesity: the insulin paradox'''
'''The response to a meal in obesity: the insulin paradox'''


Indeed, all consumers of refined starches, soft drings, high-fructose corn syrups and other energy-replete products are not born equal. Obese persons, after a meal, appear to burn less efficiently carbohydrates and even more poorly fat.<ref name="pmid11771681">{{cite journal |author=Lopes IM, Forga L, Martínez JA |title=Effects of leptin resistance on acute fuel metabolism after a high carbohydrate load in lean and overweight young men |journal=J Am Coll Nutr |volume=20 |issue=6 |pages=643–8 |year=2001 |month=December |pmid=11771681 |url=http://www.jacn.org/cgi/content/full/20/6/643}} (Free full text)</ref> A contribution of leptin resistance was suggested, since leptin was higher in the obese men that were the least efficient metabolisers of fat. However, the arrow of causality may actually be oriented in the other direction. In persons with a stronger family history of obesity, the earliest obesogenic changes are not related to leptin, but to metabolic efficiency and to insulin status and responsiveness: subjects who are at increased risk of obesity oxidize carbohydrates more quickly, oxidize fat more slowly, and have lower insulin, consistent with a greater than usual insulin sensitivity.<ref name="pmid14970841">{{cite journal |author=Giacco R, Clemente G, Busiello L, ''et al'' |title=Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight |journal=Int. J. Obes. Relat. Metab. Disord. |volume=28 |issue=2 |pages=342–8 |year=2004 |month=February |pmid=14970841 |url=http://www.nature.com/ijo/journal/v28/n2/abs/0802589a.html}} (Free full text)</ref> These findings are in sharp contrast with those implicating obesity with the development, over the long term, of the opposite of insulin sensitivity, i.e. insulin resistance.
All consumers of refined starches, soft drinks, high-fructose corn syrups and other energy-replete products are not born equal. Obese persons, after a meal, appear to burn carbohydrates less efficiently and fat even more poorly.<ref name="pmid11771681">{{cite journal |author=Lopes IM ''et al.''|title=Effects of leptin resistance on acute fuel metabolism after a high carbohydrate load in lean and overweight young men |journal=J Am Coll Nutr |volume=20 |pages=643–8 |year=2001 |pmid=11771681 |url=http://www.jacn.org/cgi/content/full/20/6/643}}</ref> A contribution of leptin resistance was suggested, as circulating concentrations of leptin were higher in the obese men that were the least efficient metabolisers of fat. However, the arrow of causality may be oriented in the other direction. In persons with a family history of obesity, the earliest obesogenic changes are not related to leptin, but to metabolic efficiency and to insulin status and responsiveness: subjects at increased risk of obesity oxidize carbohydrates more quickly and fat more slowly, and have lower insulin, consistent with a greater insulin sensitivity.<ref name="pmid14970841">{{cite journal |author=Giacco R ''et al.'' |title=Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight |journal=Int J Obes Relat Metab Disord|volume=28|pages=342–8 |year=2004 |pmid=14970841 |url=http://www.nature.com/ijo/journal/v28/n2/abs/0802589a.html}}</ref> These findings contrast with those implicating obesity with the development, over the long term, of the opposite of insulin sensitivity, i.e. insulin resistance.


'''Magnesium'''
'''Magnesium'''
 
Obese subjects, like type II diabetics, are magnesium deficient.<ref name="pmid12701060">{{cite journal |author=Takaya J ''et al.'' |title=Intracellular magnesium of platelets in children with diabetes and obesity |journal=Metab Clin Exp|volume=52 |pages=468–71 |year=2003 |pmid=12701060}}</ref> This deficiency is intracellular, and measuring intracellular magnesium requires techniques not yet available in routine clinical settings. Magnesium is required in more than 300 enzymatic reactions, including several that are rate-limiting in carbohydrate utilization. Insulin action depends on magnesium availability in cells and high glucose exposure leads to magnesium depletion and insulin resistance. In obese children, magnesium deficiency precedes insulin resistance<ref name="pmid12701060"/>, but how the heightened responsivity of cells to insulin, that is characteristic of the pre-obese state,<ref name="pmid14970841"/> relates to magnesium deficiency is not known.
Magnesium is involved early in the development of obesity. Obese subjects, like type II diabetics, are magnesium deficient.<ref name="pmid12701060">{{cite journal |author=Takaya J, Higashino H, Kotera F, Kobayashi Y |title=Intracellular magnesium of platelets in children with diabetes and obesity |journal=Metab. Clin. Exp. |volume=52 |issue=4 |pages=468–71 |year=2003 |month=April |pmid=12701060 }} Note that this deficiency is intracellular, and that most of magnesium is present in cells. Measuring intracellular magnesium requires techniques that are not yet available in routine clinical settings.</ref> Magnesium is required in more than 300 enzymatic reactions, including several that are rate-limiting in carbohydrate utilization. Insulin action is closely dependent on magnesium availability in cells and, conversely, high glucose exposure leads to magnesium depletion and insulin resistance. In obese children, magnesium deficiency precedes insulin resistance<ref name="pmid12701060"/>, but how the heightened responsivity of cells to insulin, that is characteristic of the pre-obese state,<ref name="pmid14970841"/> relates to magnesium deficiency is not known.


'''Oxidative stress and reductant stress'''
'''Oxidative stress and reductant stress'''


At the scale of the fat cells, we are facing a paradox similar to the one involving insulin. Obesity may present associated with a range of anormalities: insulin resistance, chronic inflammation, oxidative stress and a range of ills aggregating in what has been called the metabolic syndrome. It thus appears reasonable to assume that fat cells, in obesity, are in a state of oxidative stress. However, studying obesity in isolation, it became apparent that obesity at the fat cell level required the opposite of oxidative stress, e.g. a balance between oxidants and reductants tilted in favour of the latter.<ref name="pmid16377639">{{cite journal |author=Galinier A, Carrière A, Fernandez Y, ''et al'' |title=Adipose tissue proadipogenic redox changes in obesity |journal=J. Biol. Chem. |volume=281 |issue=18 |pages=12682–7 |year=2006 |month=May |pmid=16377639 |url=http://www.jbc.org/cgi/content/full/281/18/12682}}(Free full text)</ref>
At the scale of the adipocyte, we are facing a paradox similar to the one involving insulin. Obesity may present associated with a range of abnormalities: insulin resistance, chronic inflammation, oxidative stress and a range of ills aggregating in what has been called the metabolic syndrome. It thus appears reasonable to assume that adipocytes, in obesity, are in a state of oxidative stress. However, studying obesity in isolation, it became apparent that obesity at the adipocyte level required the opposite of oxidative stress, e.g. a balance between oxidants and reductants tilted in favour of the latter.<ref name="pmid16377639">{{cite journal |author=Galinier A ''et al.'' |title=Adipose tissue proadipogenic redox changes in obesity |journal=J Biol Chem|volume=281 |pages=12682–7|year=2006 |pmid=16377639 |url=http://www.jbc.org/cgi/content/full/281/18/12682}}</ref>


'''Omega-6 vs. omega-3 unsaturated fatty acids'''
'''Omega-6 vs. omega-3 unsaturated fatty acids'''


The amount of fat to which fat cells are exposed condition their development. The type of fat also is a determinant of fat cell growth (hypertrophy) and multiplication (hyperplasia), a factor that has been largely disregarded until recently. The amount of omega-6 fatty acids in the diet, in absolute terms as well as relative to the amounts of omega-3 fatty acids, have risen sharply since 1945 due to the invention of novel techniques to extract fat from vegetable sources. Omega-6 fatty acids, as a [[prostacyclin]] precursors, enhance [[cyclic AMP]]-dependent signaling pathways in preadipocytes and promote the development of mature adipocytes. Only by modulating the proportion of omega-6 fatty acids in the diet (without increasing total caloric intake), it is possible to cause in animals a 50% increase in body mass.<ref name="pmid12576509">{{cite journal |author=Massiera F, Saint-Marc P, Seydoux J, ''et al'' |title=Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? |journal=J. Lipid Res. |volume=44 |issue=2 |pages=271–9 |year=2003 |month=February |pmid=12576509 |url=http://www.jlr.org/cgi/content/full/44/2/271}} (Free full text)</ref>
The amount and type of fat to which adipocytes are exposed conditions their development. The amount of omega-6 fatty acids in the diet, in absolute terms as well as relative to the amounts of omega-3 fatty acids, have risen sharply since 1945 due to novel techniques to extract fat from vegetable sources. Omega-6 fatty acids, as a [[prostacyclin]] precursors, enhance [[cyclic AMP]]-dependent signaling pathways in preadipocytes and promote the development of mature adipocytes. Only by modulating the proportion of omega-6 fatty acids in the diet (without increasing total caloric intake), it is possible to cause in animals a 50% increase in body mass.<ref name="pmid12576509">{{cite journal |author=Massiera F ''et al.'' |title=Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern? |journal=J Lipid Res |volume=44 |pages=271–9 |year=2003 |pmid=12576509 |url=http://www.jlr.org/cgi/content/full/44/2/271}}</ref>


'''New insights'''
As research advances, it will be possible to evaluate the relative contributions of various factors and identify the most crucial steps leading to obesity. Until recently, it was exceedingly difficult to differenciate between changes that resulted from obesity and those that led to this pathological change: the failure of leptin therapy is a good illustration of the problem (see [[adipocyte]] for details). New methodologies are developped to track and identify the most crucial obesogenic changes.


'''''Starving in a sea of plenty'''''
'''''Starving in a sea of plenty'''''


In March 2008, the [[Public Library of Sciences]] journal published a [[twin study]] that carefully selected, out of a pool of 2,453 young healthy twin pairs, 14 pairs of twins that were discordant for obesity (one twin being obese, and the other not).<ref name="pmid18336063">{{cite journal |author=Pietiläinen KH, Naukkarinen J, Rissanen A, ''et al'' |title=Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity |journal=PLoS Med. |volume=5 |issue=3 |pages=e51 |year=2008 |month=March |pmid=18336063 |url=http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050051&ct=1#toclink5}}</ref> This study design allowed to rule out all genetic factors, as well as intrauterine influences and several environmental factors commonly shared amongst siblings of similar ages. The most significant changes that were found in adipocytes were a sharp decrease in the number of mitochondria, the power plants of the cells that are involved in fat burning, and a specific decrease in their ability to oxidize (burn) three amino acids called [[branched-chain amino acids]], that are the first amino acids to be used as fuel when other sources are unavailable. These amino acids, being poorly catabolized, were higher in the circulation; this signalled the release of higher amounts of more insulin, possibly leading to a vicious cycle. Considering metabolic pathways that were, on the contrary, up-regulated, the Finnish researchers found that numerous known and lesser-known inflammatory cascades were overactive. The sharp decline in the number of mitochondria remains the most important finding, which will help to design therapies adressing the fact that, in the disease of affluent civilisations ''par excellence'', fat cells and their energy-producing organelles, the mitochondria, are "starving in a sea of plenty".
In 2008, a [[twin study]] was published which carefully selected, from 2,453 young healthy twin pairs, 14 pairs that were discordant for obesity (one twin being obese, and the other not).<ref name="pmid18336063">{{cite journal |author=Pietiläinen KH ''et al.''|title=Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity |journal=PLoS Med|volume=5|pages=e51 |year=2008 |pmid=18336063 |url=http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pmed.0050051&ct=1#toclink5}}</ref> This study ruled out all genetic factors, as well as intrauterine influences and several environmental factors commonly shared amongst siblings of similar ages. The most significant changes in adipocytes were a sharp decrease in the number of mitochondria, the power plants of the cells that are involved in fat burning, and a specific decrease in their ability to oxidize (burn) three amino acids called [[branched-chain amino acids]], that are the first amino acids to be used as fuel when other sources are unavailable. These amino acids, being poorly catabolized, were higher in the circulation; this signalled the release of higher amounts of more insulin, possibly leading to a vicious cycle. Considering metabolic pathways that were, on the contrary, up-regulated, the researchers found that numerous inflammatory cascades were overactive. The decline in the number of mitochondria remains the most important finding, which will help to design therapies addressing the fact that, in the disease of affluent civilisations ''par excellence'', adipocytes and their energy-producing organelles, the mitochondria, are "starving in a sea of plenty".


'''The gut flora of the obese: the enemy within'''  
'''The gut flora of the obese: the enemy within'''  


The gut flora, which fulfills an essential symbiotic role in animal metabolism, is probably the first victim of a high-fat diet. Before one becomes obese due to dietary excesses, the trillions of micro-organisms which inhabit our intestines have already transformed into a pro-inflammatory, obesogenic organ.<ref name="pmid18326589">{{cite journal |author=Kalliomäki M, Collado MC, Salminen S, Isolauri E |title=Early differences in fecal microbiota composition in children may predict overweight |journal=Am. J. Clin. Nutr. |volume=87 |issue=3 |pages=534–8 |year=2008 |month=March |pmid=18326589 |doi= |url=http://www.ajcn.org/cgi/pmidlookup?view=long&pmid=18326589}}</ref><ref name="pmid18305141">{{cite journal |author=Cani PD, Bibiloni R, Knauf C, ''et al'' |title=Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice |journal=Diabetes |year=2008 |month=March |pmid=18305141 |doi=10.2337/db07-1403}}</ref><ref name="pmid17456850">{{cite journal |author=Cani PD, Amar J, Iglesias MA, ''et al'' |title=Metabolic endotoxemia initiates obesity and insulin resistance |journal=Diabetes |volume=56 |issue=7 |pages=1761–72 |year=2007 |month=July |pmid=17456850 |doi=10.2337/db06-1491 |url=http://diabetes.diabetesjournals.org/cgi/content/full/56/7/1761}} (Free full text)</ref>
The gut flora, which fulfills an essential symbiotic role in animal metabolism, is probably the first victim of a high-fat diet. Before one becomes obese due to dietary excesses, the trillions of micro-organisms which inhabit our intestines have already transformed into a pro-inflammatory, obesogenic organ.<ref name="pmid18326589">{{cite journal |author=Kalliomäki M ''et al.'' |title=Early differences in fecal microbiota composition in children may predict overweight |journal=Am J Clin Nutr|volume=87|pages=534–8 |year=2008|pmid=18326589}}</ref><ref name="pmid18305141">{{cite journal |author=Cani PD ''et al.'' |title=Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice |journal=Diabetes |year=2008 |pmid=18305141}}</ref><ref name="pmid17456850">{{cite journal|author=Cani PD ''et al.'' |title=Metabolic endotoxemia initiates obesity and insulin resistance|journal=Diabetes|volume=56 |pages=1761–72|year=2007|pmid=17456850 |url=http://diabetes.diabetesjournals.org/cgi/content/full/56/7/1761}}</ref>


==Treatment==
==Treatment==
The mainstay of treatment for obesity is an energy-limited [[dieting|diet]] and increased [[Physical exercise|exercise]]. In studies, diet and exercise programs have consistently produced an average weight loss of approximately 8% of total body mass (excluding study drop-outs). While not all dieters will be satisfied with this outcome, studies have shown that a loss of as little as 5% of body mass can create large health benefits. A more intractable [[Sociotherapy|therapeutic]] problem appears to be weight loss maintenance. Of dieters who manage to lose 10% or more of their [[body mass]] in studies, 80-95% will regain that weight within two to five years, supporting the finding that the body has various mechanisms that maintain weight at a certain set point.
''See also [[Bariatric surgery]], [[Drug treatments for obesity]] and [[Exercise and body weight]]''


In a [[clinical practice guideline]] by the [[American College of Physicians]], the following five recommendations are made:<ref name=Snow2005>{{cite journal | author=Snow V, Barry P, Fitterman N, Qaseem A, Weiss K | title=Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians | journal=Ann Intern Med | year=2005 | pages=525-31 | volume=142 | issue=7 | id=PMID 15809464}} [http://www.annals.org/cgi/content/full/142/7/525 Fulltext].</ref>
The mainstay of treatment for obesity is an energy-limited [[dieting|diet]] and increased [[Physical exercise|exercise]]. In studies, diet and exercise programs have consistently produced an average weight loss of approximately 8% of total body mass (excluding study drop-outs). While not all dieters will be satisfied with this outcome, a loss of as little as 5% of body mass can create large health benefits. A more intractable [[Sociotherapy|therapeutic]] problem appears to be weight loss maintenance. Of dieters who manage to lose 10% or more of their [[body mass]] in studies, 80-95% will regain that weight within two to five years, supporting the finding that the body has various mechanisms that maintain weight at a certain set point.
# People with a BMI of over 30 should be counseled on diet, exercise and other relevant behavioral interventions, and set a realistic goal for weight loss.
 
A [[clinical practice guideline]] issued by the [[American College of Physicians]] in 2005 made five recommendations:<ref name=Snow2005>{{cite journal | author=Snow V ''et al.''| title=Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians| journal=Ann Intern Med | year=2005| pages=525-31| volume=142|id=PMID 15809464}} [http://www.annals.org/cgi/content/full/142/7/525].</ref>
# People with a BMI above 30 should be counseled on diet, exercise and other relevant behavioral interventions, and set a realistic goal for weight loss.
# If these goals are not achieved, pharmacotherapy can be offered. The patient needs to be informed of the possibility of [[Adverse effect (medicine)|side-effects]] and the unavailability of long-term safety and efficacy data.
# If these goals are not achieved, pharmacotherapy can be offered. The patient needs to be informed of the possibility of [[Adverse effect (medicine)|side-effects]] and the unavailability of long-term safety and efficacy data.
# Drug therapy may consist of [[sibutramine]], [[orlistat]], [[phentermine]], [[diethylpropion]], [[fluoxetine]], and [[bupropion]]. For more severe cases of obesity, stronger drugs such as [[amphetamine]] and [[methamphetamine]] may be used on a selective basis.  Evidence is not sufficient to recommend [[sertraline]], [[topiramate]], or [[zonisamide]].
# Drug therapy may consist of [[sibutramine]], [[orlistat]], [[phentermine]], [[diethylpropion]], [[fluoxetine]], and [[bupropion]]. For more severe cases of obesity, stronger drugs such as [[amphetamine]] and [[methamphetamine]] may be used on a selective basis.  Evidence is not sufficient to recommend [[sertraline]], [[topiramate]], or [[zonisamide]].
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# Those requiring bariatric surgery should be referred to high-volume referral centers, as the evidence suggests that surgeons who frequently perform these procedures have fewer complications.
# Those requiring bariatric surgery should be referred to high-volume referral centers, as the evidence suggests that surgeons who frequently perform these procedures have fewer complications.


A [[clinical practice guideline]] by the [[US Preventive Services Task Force]] (USPSTF) concluded that the evidence is insufficient to recommend for or against routine behavioral counseling to promote a healthy diet in unselected patients in primary care settings, but that intensive behavioral dietary counseling is recommended in those with [[hyperlipidemia]] and other known risk factors for cardiovascular and diet-related chronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians.<ref>{{cite web |url=http://www.ngc.gov/summary/summary.aspx?ss=15&doc_id=3494 |title=Behavioral counseling in primary care to promote a healthy diet: recommendations and rationale. |accessdate=2007-05-22 |format= |work=}}</ref><ref name="pmid12554027">{{cite journal |author=Pignone MP, Ammerman A, Fernandez L, ''et al'' |title=Counseling to promote a healthy diet in adults: a summary of the evidence for the U.S. Preventive Services Task Force |journal=American journal of preventive medicine |volume=24 |issue=1 |pages=75-92 |year=2003 |pmid=12554027 |doi=}}</ref>
A [[clinical practice guideline]] by the [[U.S. Preventive Services Task Force]] (USPSTF) concluded that the evidence is insufficient to recommend for or against routine behavioral counseling to promote a healthy diet in unselected patients in primary care settings, but that intensive behavioral dietary counseling is recommended in those with [[hyperlipidemia]] and other known risk factors for cardiovascular and diet-related chronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians.<ref>{{cite web |url=http://www.ngc.gov/summary/summary.aspx?ss=15&doc_id=3494 |title=Behavioral counseling in primary care to promote a healthy diet: recommendations and rationale. |accessdate=2007-05-22}}</ref><ref name="pmid12554027">{{cite journal |author=Pignone MP ''et al.'' |title=Counseling to promote a healthy diet in adults: a summary of the evidence for the U.S. Preventive Services Task Force|journal=Am J Prev Med|volume=24|pages=75-92|year=2003|pmid=12554027}}</ref>


===Counseling===
===Counseling===
A [[meta-analysis]] of [[randomized controlled trial]]s concluded that "compared with usual care, dietary counseling interventions produce modest weight losses that diminish over time."<ref name="pmid17606960">{{cite journal |author=Dansinger ML, Tatsioni A, Wong JB, Chung M, Balk EM |title=Meta-analysis: the effect of dietary counseling for weight loss |journal=Ann. Intern. Med. |volume=147 |issue=1 |pages=41-50 |year=2007 |pmid=17606960 |doi=|url=http://www.annals.org/cgi/content/full/147/1/41}}</ref>
A [[meta-analysis]] of [[randomized controlled trial]]s concluded that "compared with usual care, dietary counseling interventions produce modest weight losses that diminish over time."<ref name="pmid17606960">{{cite journal |author=Dansinger ML ''et al.'' |title=Meta-analysis: the effect of dietary counseling for weight loss|journal=Ann Intern Med |volume=147|pages=41-50 |year=2007 |pmid=17606960}}</ref>


The role of genetic counseling is unclear<ref name="pmid15216550">{{cite journal |author=Marteau T ''et al.'' |title=Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial |journal=Am. J. Med. Genet. A |volume=128  |pages=285–93 |year=2004 |pmid=15216550 |doi=10.1002/ajmg.a.30102}}</ref>; however, based on a study done of hypercholesterolemia, it is possible that genetic counseling might lead to patients preferring medication over diet therapy.<ref name="pmid17879121">{{cite journal |author=Rief W ''et al.'' |title=Is information on genetic determinants of obesity helpful or harmful for obese people?--A randomized clinical trial |journal=J Gen Intern Med |volume=22 |pages=1553–9 |year=2007 |pmid=17879121 |doi=10.1007/s11606-007-0353-7}}</ref>
The role of genetic counseling is unclear<ref name="pmid15216550">{{cite journal|author=Marteau T ''et al.'' |title=Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial |journal=Am J Med Genet A|volume=128  |pages=285–93 |year=2004 |pmid=15216550 }}</ref>; but based on a study done of hypercholesterolemia, it is possible that genetic counseling might lead to patients preferring medication over diet therapy.<ref name="pmid17879121">{{cite journal |author=Rief W ''et al.''|title=Is information on genetic determinants of obesity helpful or harmful for obese people?-A randomized clinical trial |journal=J Gen Intern Med|volume=22|pages=1553–9|year=2007|pmid=17879121}}</ref>


====Portion control plate====
====Delivery method for counseling====
A randomized controlled trial found that patients using portion control plates and log books had more weight loss and less use of hypoglycemic drugs.<ref name="pmid17592101">{{cite journal |author=Pedersen SD, Kang J, Kline GA |title=Portion control plate for weight loss in obese patients with type 2 diabetes mellitus: a controlled clinical trial |journal=Arch. Intern. Med. |volume=167 |pages=1277–83 |year=2007 |pmid=17592101 |doi=10.1001/archinte.167.12.1277 |issn=}} [http://www.acpjc.org/Content/147/3/issue/ACPJC-2007-147-3-068.htm ACP Journal Club review]</ref>
* Personal contact may better sustain weight loss<ref name="pmid18334689">{{cite journal| author=Svetkey LP, Stevens VJ, Brantley PJ, Appel LJ, Hollis JF, Loria CM et al.| title=Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial. | journal=JAMA | year= 2008 | volume= 299 | issue= 10 | pages= 1139-48 | pmid=18334689 | doi=10.1001/jama.299.10.1139 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18334689  }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18667668 Review in: Evid Based Med. 2008 Aug;13(4):109]  [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18624372 Review in: ACP J Club. 2008 Jul;149(1):4] </ref>
 
* The [[Internet]] may increase [[patient participation]] in their health care.<ref name="pmid12684363">{{cite journal| author=Tate DF, Jackvony EH, Wing RR| title=Effects of Internet behavioral counseling on weight loss in adults at risk for type 2 diabetes: a randomized trial. | journal=JAMA | year= 2003 | volume= 289 | issue= 14 | pages= 1833-6 | pmid=12684363 | doi=10.1001/jama.289.14.1833 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12684363  }} </ref><ref name="pmid18201641">{{cite journal|author=Hunter CM ''et al.''|title=Weight management using the internet a randomized controlled trial|journal=Am J Prev Med|volume=34|pages=119–26|year=2008 |pmid=18201641}}</ref>
====Internet-based counseling====
* High-frequency [[telephone]] contact may help.<ref name="pmid19221377">{{cite journal| author=Digenio AG, Mancuso JP, Gerber RA, Dvorak RV| title=Comparison of methods for delivering a lifestyle modification program for obese patients: a randomized trial. | journal=Ann Intern Med | year= 2009 | volume= 150 | issue= 4 | pages= 255-62 | pmid=19221377 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19221377  }} </ref>
The [[Internet]] offer a method to increase [[patient participation]] in their health care. A randomized controlled trial showed some benefit in a weight loss program that used the Internet.<ref name="pmid18201641">{{cite journal |author=Hunter CM, Peterson AL, Alvarez LM, ''et al'' |title=Weight management using the internet a randomized controlled trial |journal=Am J Prev Med |volume=34 |issue=2 |pages=119–26 |year=2008 |pmid=18201641 |doi=10.1016/j.amepre.2007.09.026}}</ref>


===Diets===
===Diets===
{|align="right" class="wikitable"
{{main|Diet (weight loss)}}
|+ Descriptions of common diets
! Diet!! Description
|-
| [[American Heart Association]] diet<ref name="pmid11056107">{{cite journal |author=Krauss RM, Eckel RH, Howard B, ''et al'' |title=AHA Dietary Guidelines: revision 2000: A statement for healthcare professionals from the Nutrition Committee of the American Heart Association |journal=Circulation |volume=102 |issue=18 |pages=2284–99 |year=2000 |month=October |pmid=11056107 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=11056107 |issn=}}</ref> || low fat
|-
| [[Atkins diet|Dr Atkins' diet]] || Carbohydrate-restricted<br> initially < 20 g of carbohydrate daily, subsequently  50 g/day
|-
| [[LEARN diet]] || low fat
|-
| [[Mediterranean diet]]<ref name="isbn0-7432-6642-0">{{cite book |author= |authorlink= |editor= |others= |title=Eat, Drink, and Be Healthy : The Harvard Medical School Guide to Healthy Eating |edition= |language= |publisher=Free Press |location=New York |year=2005 |origyear= |pages= |quote= |isbn=0-7432-6642-0 |oclc= |doi= |url= |accessdate=|id={{LCC| RA784 .W635}}}}</ref> || moderate-fat (<35% of calories) emphasizing monounsaturated fats
|-
| [[Ornish diet]] || vegetarian, low fat
|-
| [[Rosemary Conley]] || low-fat and social support
|-
| [[Slim-Fast]] plan || low glycemic index
|-
| [[SouthBeach diet]] plan || Carbohydrate-restricted; meal replacement
|-
| [[Weight Watchers]] || balanced diet with social support
|-
| [[Zone diet]] || low-carbohydrate diet<br> carbohydrates, proteins, and fats in 40:30:30 ratio
|}
 
The [[United States]] [[Department of Health and Human Services]] and [[Department of Agriculture]] jointly recommend:<ref>{{cite web |url=http://www.health.gov/dietaryguidelines/dga2005/recommendations.htm |title=Key Recommendations for the General Population, Dietary Guidelines for Americans 2005 |author= |authorlink= |coauthors= |date=2005 |format= |work= |publisher=United States Department of Agriculture |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2008-07-01}}</ref>
* "Keep total fat intake between 20 to 35 percent of calories."
** "Consume less than 10 percent of calories from saturated fatty acids"
** "Less  than 300 mg/day of cholesterol"
** "Keep trans fatty acid consumption as low as  possible"
* "The Average Macronutrient Distribution Range (AMDR) for carbohydrates is 45  to 65 percent of total calories."
** "The recommended [[dietary fiber]] intake is 14 grams per 1,000 calories consumed."
 
MyPyramid.gov offer online dietary support at http://www.mypyramidtracker.gov/.
 
Various alternative dietary approaches have been proposed, some of which have been compared by [[randomized controlled trial]]s:
* A comparison of [[Atkins diet|Dr Atkins' diet]], [[Slim-Fast]] plan, [[Weight Watchers]] "pure points programme", and [[Rosemary Conley]]'s found no significant differences.<ref name="pmid16720619">{{cite journal |author=Truby H ''et al.'' |title=Randomised controlled trial of four commercial weight loss programmes in the UK: initial findings from the BBC "diet trials" |journal=BMJ |volume=332 |pages=1309-14 |year=2006 |pmid=16720619 |doi=10.1136/bmj.38833.411204.80}}</ref>
* A comparison of Atkins, [[Zone diet]], [[Ornish diet]], and [[LEARN diet]] in ''premenopausal women'' found the greatest benefit from the [[Atkins diet]].<ref name="pmid17341711">{{cite journal |author=Gardner CD ''et al'' |title=Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial |journal=JAMA |volume=297  |pages=969-77 |year=2007 |pmid=17341711 |doi=10.1001/jama.297.9.969}}</ref>
* A comparison of [[Atkins diet]], [[Zone diet]], [[Weight Watchers]], and [[Ornish diet]] noted:<ref name="pmid15632335">{{cite journal |author=Dansinger ML, Gleason JA, Griffith JL, Selker HP, Schaefer EJ |title=Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial |journal=JAMA |volume=293 |issue=1 |pages=43-53 |year=2005 |pmid=15632335 |doi=10.1001/jama.293.1.43}}</ref>
: "all 4 diets resulted in modest statistically significant weight loss at 1 year, with no statistically significant differences between diets"
: "The higher discontinuation rates for the Atkins and Ornish diet groups suggest many individuals found these diets to be too extreme"
* A comparison of three diets: 1) low-fat, restricted-calorie; 2) Mediterranean, restricted-calorie; or 3) low-carbohydrate, non-restricted-calorie found:<ref name="pmid18635428">{{cite journal |author=Shai I, Schwarzfuchs D, Henkin Y, ''et al'' |title=Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet |journal=N. Engl. J. Med. |volume=359 |issue=3 |pages=229–41 |year=2008 |month=July |pmid=18635428 |doi=10.1056/NEJMoa0708681 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18635428&promo=ONFLNS19 |issn=}}</ref>
** ''Least weight'' loss occurred in the low-fat, restricted-calorie group
** More favorable effects on lipids with the low-carbohydrate diet
** More favorable effects on glycemic control with the Mediterranean diet
 
====Carbohydrate-restricted (low carbohydrate) versus fat-restricted (low fat) diets====
Many studies have focused on diets that reduce calories via a low-carbohydrate ([[Atkins diet]], [[South Beach diet]],  [[Zone diet]]) diet (< 20-30 grams/day of carbohydrate) versus a low-fat diet ([[LEARN diet]], [[Ornish diet]]).
 
The [[Nurses' Health Study]], an observational [[cohort study]], found that low carbohydrate diets based on vegetable sources of fat and protein are associated with less [[coronary heart disease]].<ref name="pmid17093250">{{cite journal |author=Halton TL ''et al.'' |title=Low-carbohydrate-diet score and the risk of coronary heart disease in women |journal=N Engl J Med |volume=355 |pages=1991-2002 |year=2006 |pmid=17093250 |doi=10.1056/NEJMoa055317}}</ref>
 
* A comparison of three diets: 1) low-fat, restricted-calorie; 2) Mediterranean, restricted-calorie; or 3) low-carbohydrate, non-restricted-calorie found:<ref name="pmid18635428">{{cite journal |author=Shai I, Schwarzfuchs D, Henkin Y, ''et al'' |title=Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet |journal=N. Engl. J. Med. |volume=359 |issue=3 |pages=229–41 |year=2008 |month=July |pmid=18635428 |doi=10.1056/NEJMoa0708681 |url=http://content.nejm.org/cgi/pmidlookup?view=short&pmid=18635428&promo=ONFLNS19 |issn=}}</ref>
** ''Least weight'' loss occurred in the low-fat, restricted-calorie group
** More favorable effects on lipids with the low-carbohydrate diet
** More favorable effects on glycemic control with the Mediterranean diet
 
A [[meta-analysis]] that included older [[randomized controlled trial]]s<ref name="pmid12761364">{{cite journal |author=Samaha FF, Iqbal N, Seshadri P, ''et al'' |title=A low-carbohydrate as compared with a low-fat diet in severe obesity |journal=N. Engl. J. Med. |volume=348 |issue=21 |pages=2074–81 |year=2003 |pmid=12761364 |doi=10.1056/NEJMoa022637}}</ref><ref name="pmid12761365">{{cite journal |author=Foster GD ''et al.'' |title=A randomized trial of a low-carbohydrate diet for obesity |journal=N Engl J Med |volume=348  |pages=2082–90 |year=2003 |pmid=12761365 |doi=10.1056/NEJMoa022207}}</ref><ref name="pmid15632335"/> (but not the two more recent studies above) found:<ref name="pmid16476868">{{cite journal |author=Nordmann AJ ''et al.'' |title=Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials |journal=Arch. Intern. Med. |volume=166  |pages=285-93 |year=2006 |pmid=16476868 |doi=10.1001/archinte.166.3.285}}</ref>
:"low-carbohydrate, non-energy-restricted diets appear to be at least as effective as low-fat, energy-restricted diets in inducing weight loss for up to 1 year. However, potential favorable changes in triglyceride and high-density lipoprotein cholesterol values should be weighed against potential unfavorable changes in low-density lipoprotein cholesterol values when low-carbohydrate diets to induce weight loss are considered."
 
An older [[meta-analysis]] of [[randomized controlled trial]]s by the [[Cochrane Collaboration]] in 2002 concluded<ref name="pmid12076496">{{cite journal |author=Pirozzo S ''et al.'' |title=Advice on low-fat diets for obesity |journal=Cochrane database of systematic reviews (Online) |volume=  |pages=CD003640 |year=2002 |pmid=12076496 |doi=}}</ref> that fat-restricted diets are no better than calorie restricted diets in achieving long term weight loss in overweight or obese people.
 
The [[Women's Health Initiative]] Randomized Controlled Dietary Modification Trial<ref name="pmid16391215">{{cite journal |author=Howard BV ''et al.'' |title=Low-fat dietary pattern and weight change over 7 years: the Women's Health Initiative Dietary Modification Trial |journal=JAMA |volume=295 |pages=39-49 |year=2006 |pmid=16391215 |doi=10.1001/jama.295.1.39}}</ref> found that a diet of total fat to 20% of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily:
* no reduction in cardiovascular disease<ref name="pmid16467234">{{cite journal |author=Howard BV ''et al.'' |title=Low-fat dietary pattern and risk of cardiovascular disease: the Women's Health Initiative Randomized Controlled Dietary Modification Trial |journal=JAMA |volume=295  |pages=655-66 |year=2006 |pmid=16467234 |doi=10.1001/jama.295.6.655}}</ref>
* an insignificant reduction in invasive breast cancer<ref name="pmid16467232">{{cite journal |author=Prentice RL, Caan B, Chlebowski RT, ''et al'' |title=Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial |journal=JAMA |volume=295 |issue=6 |pages=629-42 |year=2006 |pmid=16467232 |doi=10.1001/jama.295.6.629}}</ref>
* no reductions in colorectal cancer<ref name="pmid16467233">{{cite journal |author=Beresford SA ''et al.'' |title=Low-fat dietary pattern and risk of colorectal cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial |journal=JAMA |volume=295  |pages=643-54 |year=2006 |pmid=16467233 |doi=10.1001/jama.295.6.643}}</ref>
 
Additional recent [[randomized controlled trial]]s have found that:
* A comparison of Atkins, [[Zone diet]], [[Ornish diet]], and [[LEARN diet]] in ''premenopausal women'' found the greatest benefit from the [[Atkins diet]].<ref name="pmid17341711">{{cite journal |author=Gardner CD ''et al'' |title=Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial |journal=JAMA |volume=297  |pages=969-77 |year=2007 |pmid=17341711 |doi=10.1001/jama.297.9.969}}</ref>


* The choice of diet for a specific person may be influenced by measuring the invididual's insulin secretion:
====Portion control====
:In [[young adults]] "Reducing glycemic [carbohydrate] load may be especially important to achieve weight loss among individuals with high insulin secretion."<ref name="pmid17507345">{{cite journal |author=Ebbeling CB ''et al.''|title=Effects of a low-glycemic load vs low-fat diet in obese young adults: a randomized trial |journal=JAMA |volume=297  |pages=2092-102 |year=2007 |pmid=17507345 |doi=10.1001/jama.297.19.2092}}</ref> This is consistent with prior studies of diabetic patients in which low carbohydrate diets were more beneficial.<ref name="pmid15148064">{{cite journal |author=Stern ''et al.'' |title=The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial |journal=Ann Intern Med |volume=140|pages=778–85 |year=2004 |pmid=15148064 |doi=}}</ref><ref name="pmid7848401">{{cite journal |author=Garg A ''et al.'' |title=Effects of varying carbohydrate content of diet in patients with non-insulin-dependent diabetes mellitus |journal=JAMA |volume=271 |pages=1421–8 |year=1994 |pmid=7848401 |doi=}}</ref>
A randomized controlled trial found that patients using portion control plates and log books had more weight loss and less use of hypoglycemic drugs.<ref name="pmid17592101">{{cite journal |author=Pedersen SD ''et al.''|title=Portion control plate for weight loss in obese patients with type 2 diabetes mellitus: a controlled clinical trial |journal=Arch Intern Med|volume=167|pages=1277–83 |year=2007|pmid=17592101}}[http://www.acpjc.org/Content/147/3/issue/ACPJC-2007-147-3-068.htm ACP Journal Club review]</ref>


====Low glycemic index and low glycemic load diets====
====Drink more water====
;Physiology
Encouraging more water drinking may help.<ref name="pmid19336356">{{cite journal|author=Muckelbauer R ''et al.''|title=Promotion and provision of drinking water in schools for overweight prevention: randomized, controlled cluster trial|journal=Pediatrics|volume=123|pages=e661–7|year=2009|pmid=19336356|url=http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&pmid=19336356}}</ref>
"The glycaemic index factor is a ranking of foods based on their overall effect on blood sugar levels. Low glycaemic index foods, such as lentils, provide a slower more consistent source of glucose to the bloodstream, thereby stimulating less insulin release than high glycaemic index foods, such as white bread."<ref name="pmid17636786">{{cite journal |author=Thomas D, Elliott E, Baur L |title=Low glycaemic index or low glycaemic load diets for overweight and obesity |journal=Cochrane Database Syst Rev |volume=3 |issue= |pages=CD005105 |year=2007 |pmid=17636786 |doi=10.1002/14651858.CD005105.pub2}}</ref><ref name="pmid6259925">{{cite journal |author=Jenkins DJ ''et al.'' |title=Glycemic index of foods: a physiological basis for carbohydrate exchange |journal=Am. J. Clin. Nutr. |volume=34 |pages=362-6 |year=1981 |pmid=6259925 |doi=}}</ref>


The glycemic load is "the mathematical product of the glycemic index and the carbohydrate amount".<ref name="pmid12949357">{{cite journal |author=Brand-Miller JC ''et al.'' |title=Physiological validation of the concept of glycemic load in lean young adults |journal=J Nutr |volume=133  |pages=2728-32 |year=2003 |pmid=12949357 |doi=}}</ref>
====Financial incentives====
Financial incentives may help.<ref name="pmid19066383">{{cite journal |author=Volpp KG ''et al.''|title=Financial incentive-based approaches for weight loss: a randomized trial|journal=JAMA |volume=300 |pages=2631–7|year=2008 |pmid=19066383|url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=19066383}}</ref>


;Evidence
===Food labeling===
A [[meta-analysis]] by the [[Cochrane Collaboration]] concluded that low glycemic index or low glycemic load diets led to more weight loss and better lipid profiles. ''However'', the [[Cochrane Collaboration]] grouped low glycemic index and low glycemic load diets together and did not try to separate the effects of the load versus the index.<ref name="pmid17636786">{{cite journal |author=Thomas DE, Elliott E, Baur L |title=Low glycaemic index or low glycaemic load diets for overweight and obesity |journal=Cochrane database of systematic reviews (Online) |volume=  |pages=CD005105 |year=2007 |pmid=17636786 |doi=10.1002/14651858.CD005105.pub2}}</ref>
The Nutrition Labeling and Education Act (NLEA) of 1990 went into effect in 1994 to require labeling on on packaged foods.


In a [[randomized controlled trial]] that compared four diets that varied in carbohydrate amount and glycemic index found complicated results<ref name="pmid16864756">{{cite journal |author=McMillan-Price J ''et al.'' |title=Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial |journal=Arch. Intern. Med. |volume=166 |pages=1466-75 |year=2006 |pmid=16864756 |doi=10.1001/archinte.166.14.1466}}</ref>:
New York City required labeling by restaurants with 15 or more outlets to post caloric content starting July, 2008.<ref name="pmid20375399">{{cite journal| author=Nestle M| title=Health care reform in action--calorie labeling goes national. | journal=N Engl J Med | year= 2010 | volume= 362 | issue= 25 | pages= 2343-5 | pmid=20375399 | doi=10.1056/NEJMp1003814 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20375399  }} </ref> The New York law may increase awareness of calories.<ref name="pmid19808705">{{cite journal| author=Elbel B, Kersh R, Brescoll VL, Dixon LB| title=Calorie labeling and food choices: a first look at the effects on low-income people in New York City. | journal=Health Aff (Millwood) | year= 2009 | volume= 28 | issue= 6 | pages= w1110-21 | pmid=19808705 | doi=10.1377/hlthaff.28.6.w1110 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808705 }} </ref><ref name="pmid20966367">{{cite journal| author=Dumanovsky T, Huang CY, Bassett MT, Silver LD| title=Consumer awareness of fast-food calorie information in New York City after implementation of a menu labeling regulation. | journal=Am J Public Health | year= 2010 | volume= 100 | issue= 12 | pages= 2520-5 | pmid=20966367 | doi=10.2105/AJPH.2010.191908 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20966367  }} </ref>
* Diet 1 and 2 were high carbohydrate (55% of total energy intake)
** Diet 1 was high-glycemic index
** Diet 2 was low-glycemic index
* Diet 3 and 4 were high protein (25% of total energy intake)
** Diet 3 was high-glycemic index
** Diet 4 was low-glycemic index


Diets 2 and 3 lost the most weight and fat mass; however, low density lipoprotein fell in Diet 2 and rose in Diet 3. Thus the authors concluded that the high-carbohydrate, low-glycemic index diet was the most favorable.
Public Law 111-147, the Patient Protection and Affordable Care Act, mandates that restaurants with 20 or more outlets nationwide post caloric information “in a clear and conspicuous manner.”<ref name="pmid20375399">{{cite journal| author=Nestle M| title=Health care reform in action--calorie labeling goes national. | journal=N Engl J Med | year= 2010 | volume= 362 | issue= 25 | pages= 2343-5 | pmid=20375399 | doi=10.1056/NEJMp1003814 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20375399 }} </ref>


===Exercise===
===Medications===
A [[meta-analysis]] of [[randomized controlled trial | randomized controlled trials]] by the international [[Cochrane Collaboration]] found that "exercise combined with diet resulted in a greater weight reduction than diet alone".<ref name="pmid17054187">{{cite journal |author=Shaw K ''et al.'' |title=Exercise for overweight or obesity |journal=Cochrane database of systematic reviews (Online) |volume=  |pages=CD003817 |year=2006 |pmid=17054187 |doi=10.1002/14651858.CD003817.pub3}}</ref>
{{main|Drug treatments for obesity}}
 
Use of a pedometer may assist in exercising for weight loss.<ref name="pmid18195317">{{cite journal |author=Richardson CR ''et al.'' |title=A meta-analysis of pedometer-based walking interventions and weight loss |journal=Ann Fam Med  |issue=1 |pages=69–77 |year=2008 |pmid=18195317 |doi=10.1370/afm.761}}</ref>
 
===Drugs===
A systematic review found that the average weight loss after at least one year was:<ref name="pmid18006966">{{cite journal |author=Rucker D, Padwal R, Li SK, Curioni C, Lau DC |title=Long term pharmacotherapy for obesity and overweight: updated meta-analysis |journal=BMJ |volume= |issue= |pages= |year=2007 |pmid=18006966 |doi=10.1136/bmj.39385.413113.25}}</ref>
* [[Orlistat]]:  2.9 kg, but produced  gastrointestinal side effects.
* [[Sibutramine]]: 4.2 kg, but raised blood pressure and pulse.
* [[Rimonabant]]: 4.7-kg, but associated with increased  psychiatric disorders. About a third of patients discontinued treatment.<ref name="pmid18022033">{{cite journal |author=Christensen R ''et al.'' |title=Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials |journal=Lancet |volume=370 |issue=9600 |pages=1706–13 |year=2007 |pmid=18022033 |doi=10.1016/S0140-6736(07)61721-8 |issn=}}</ref><ref name="pmid18006966"/>
 
For patients with [[diabetes mellitus type 2]], [[metformin]] (Glucophage) can assist in weight loss—rather than [[sulfonylurea]] derivatives and [[insulin]], which often lead to further weight gain.  The [[thiazolidinedione]]s ([[rosiglitazone]] or [[pioglitazone]]) can cause slight weight gain, but decrease the "pathologic" form of abdominal fat, and so may help obese diabetics.


===Bariatric surgery===
===Bariatric surgery===
{{main|Bariatric surgery}}
''[[Bariatric surgery]]'' (or "weight loss surgery") is the use of surgical interventions in the treatment of obesity. As every surgical intervention may lead to complications, it is regarded as a last resort when dietary modification and pharmacological treatment have proven to be unsuccessful.
''[[Bariatric surgery]]'' (or "weight loss surgery") is the use of surgical interventions in the treatment of obesity. As every surgical intervention may lead to complications, it is regarded as a last resort when dietary modification and pharmacological treatment have proven to be unsuccessful.
 
In the U.S.A.,[[Medicare]] will only only pay for procedures performed at approved facilities.<ref name="urlBariatric Surgery">{{cite web |url=http://www.cms.hhs.gov/MedicareApprovedFacilitie/BSF/|title=Bariatric Surgery |publisher=Centers for Medicare & Medicaid Services|accessdate=2008-06-26}}</ref>
In the [[United States]], [[Medicare]] will only only pay for procedures performed at approved facilities.<ref name="urlBariatric Surgery">{{cite web |url=http://www.cms.hhs.gov/MedicareApprovedFacilitie/BSF/ |title=Bariatric Surgery |publisher=Centers for Medicare & Medicaid Services|format= |work= |accessdate=2008-06-26}}</ref>
 
====Types of surgery====
Weight loss surgery relies on various principles.  Band surgery is reversible, while bowel shortening operations are not. Some procedures can be performed [[laparoscopic surgery|laparoscopically]].
 
* '''Predominantly restrictive procedures'''. The most common approaches are reducing the volume of the stomach, producing an earlier sense of satiation (e.g. by [[adjustable gastric band]]ing and [[Vertical banded gastroplasty surgery|vertical banded gastroplasty]]).
* '''Predominantly restrictive procedures'''. The most common approaches are reducing the volume of the stomach, producing an earlier sense of satiation (e.g. by [[adjustable gastric band]]ing and [[Vertical banded gastroplasty surgery|vertical banded gastroplasty]]).
* '''Predominantly malabsorptive procedures''' Others procedures also reduce the length of bowel that food will be in contact with, directly reducing absorption ([[gastric bypass surgery]]).
* '''Predominantly malabsorptive procedures''' Others procedures also reduce the length of bowel that food will be in contact with, directly reducing absorption ([[gastric bypass surgery]]).


====Complications====
Band surgery is reversible, while gastric bypass surgery is not. In general, gastric bypass surgery leads to more weight loss than band surgery. A [[meta-analysis]] by the [[American College of Physicians]] reports the following weight loss at 36 months:<ref name="pmid15809466">{{cite journal |author=Maggard MA ''et al.''|title=Meta-analysis: surgical treatment of obesity|journal=Ann Intern Med|volume=142|pages=547–59|year=2005|pmid=15809466}}</ref>
Complications from weight loss surgery are frequent.<ref name="pmid16862031">{{cite journal |author=Encinosa WE ''et al.''|title=Healthcare utilization and outcomes after bariatric surgery |journal=Medical Care |volume=44  |pages=706-12 |year=2006 |pmid=16862031 |doi=10.1097/01.mlr.0000220833.89050.ed}}</ref> The reduction in intestinal absorptive capacity may cause, for instance, persistent anemia only reversible though the intravenous route.<ref name="pmid17352964">{{cite journal |author=Mizón C ''et al.'' |title=Persistent anemia after Roux-en-Y gastric bypass |journal=Nutrition |volume=23 |pages=277–80 |year=2007 |pmid=17352964 |doi=10.1016/j.nut.2007.01.008}}</ref>
 
====Effectiveness of surgery====
=====Weight loss=====
In general, the malabsorptive procedures lead to more weight loss than the restrictive procedures. A [[meta-analysis]] by the [[American College of Physicians]] reports the following weight loss at 36 months:<ref name="pmid15809466">{{cite journal |author=Maggard MA ''et al.'' |title=Meta-analysis: surgical treatment of obesity |journal=Ann. Intern. Med. |volume=142 |pages=547–59 |year=2005 |pmid=15809466 |doi=}}</ref>
* Biliopancreatic diversion - 53 kg
* Biliopancreatic diversion - 53 kg
* Roux-en-Y gastric bypass (RYGB) - 41 kg
* Roux-en-Y gastric bypass - 41 kg (Open - 42 kg; Laparoscopic - 38 kg)
** Open - 42 kg
** Laparoscopic - 38 kg
* Adjustable gastric banding - 35 kg
* Adjustable gastric banding - 35 kg
* Vertical banded gastroplasty - 32 kg
* Vertical banded gastroplasty - 32 kg


=====Mortality=====
This analysis does not include a more recent [[randomized controlled trial]].<ref>Nguyen NT ''et al.'' (2009)[http://journals.lww.com/annalsofsurgery/Abstract/2009/10000/A_Prospective_Randomized_Trial_of_Laparoscopic.14.aspx A prospective randomized trial of laparoscopic gastric bypass versus laparoscopic adjustable gastric banding for the treatment of morbid obesity: Outcomes, quality of life, and costs] ''Ann Surg'' 250:631-41}}</ref>
Two studies report decrease in mortality from bariatric surgery.<ref name="pmid17715408">{{cite journal |author=Sjöström L ''et al.'' |title=Effects of bariatric surgery on mortality in Swedish obese subjects |journal=N Engl J Med |volume=357 |pages=741-52 |year=2007 |pmid=17715408 |doi=10.1056/NEJMoa066254}}</ref><ref name="pmid17715409">{{cite journal |author=Adams TD ''et al.'' |title=Long-term mortality after gastric bypass surgery |journal=N Engl J Med |volume=357  |pages=753-61 |year=2007 |pmid=17715409 |doi=10.1056/NEJMoa066603}}</ref> In the Swedish [[randomized controlled trial]], patients with a [[body mass index]] of 34 or more for men and 38 or more for women underwent various types of bariatric surgery and were followed for a mean of 11 years. Surgery patients had 5.0% mortality while control patients had 6.3% mortality. This means 75 patients must be treated to avoid one death after 11 years ([[number needed to treat]] is 77).<ref name="pmid17715408"/> In a Utah retrospective [[cohort study]] that followed patients for a mean of 7 years after various types of gastric bypass, surgery patients had 0.4% mortality while control patients had 0.6% mortality.<ref name="pmid17715409"/>


=====Remission of diabetes=====
Two studies report decreases in mortality from bariatric surgery.<ref name="pmid17715408">{{cite journal|author=Sjöström L ''et al.''|title=Effects of bariatric surgery on mortality in Swedish obese subjects |journal=N Engl J Med|volume=357|pages=741-52|year=2007|pmid=17715408 |doi=10.1056/NEJMoa066254}}</ref><ref name="pmid17715409">{{cite journal |author=Adams TD ''et al.'' |title=Long-term mortality after gastric bypass surgery |journal=N Engl J Med |volume=357|pages=753-61 |year=2007 |pmid=17715409 }}</ref> In the Swedish [[randomized controlled trial]], patients with a BMI of 34 or more for men and 38 or more for women underwent various types of bariatric surgery and were followed for a mean of 11 years. Surgery patients had 5% mortality while control patients had 6.3% mortality. <ref name="pmid17715408"/> In a Utah retrospective [[cohort study]] that followed patients for a mean of 7 years after various types of gastric bypass, surgery patients had 0.4% mortality while control patients had 0.6% mortality.<ref name="pmid17715409"/>
Bariatric surgery remits [[diabetes mellitus type 2]] in more than 1 of every two people after 2 years if they are similar to the patients in the [[randomized controlled trial]] / [[meta-analysis]] by Dixon ''et al.'' ([[Number needed to treat]] is 1.7).<ref name="pmid18212316">{{cite journal |author=Dixon JB, O'Brien PE, Playfair J, ''et al'' |title=Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial |journal=JAMA |volume=299 |issue=3 |pages=316–23 |year=2008 |month=January |pmid=18212316 |doi=10.1001/jama.299.3.316 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18212316 |issn=}}</ref>  In this trial 73% of the patients who remitted their diabetes versus 13% of the patients in the control group.
 
Bariatric surgery remits [[diabetes mellitus type 2]] in more than 1 of every two people after 2 years if they are similar to the patients in the [[randomized controlled trial]] by Dixon ''et al.''.<ref name="pmid18212316">{{cite journal |author=Dixon JB ''et al.'' |title=Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial |journal=JAMA |volume=299 |pages=316–23 |year=2008 |pmid=18212316 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=18212316}}</ref>  In this trial, 73% of the patients remitted their diabetes versus 13% of the patients in the control group.


==Prevention==
==Prevention==
Display of calorie information on the menus or menu boards of restaurants has been proposed by the city of New York.<ref name="nyt">Rivera R. (2007) “New York City Reintroduces Calorie Rule,” The New York Times, October 25, 2007, http://www.nytimes.com/2007/10/25/nyregion/25calories.html (accessed October 26, 2007).</ref>
Display of calorie information on the menus or menu boards of restaurants has been proposed by the city of New York.<ref name="nyt">Rivera R (2007) “New York City Reintroduces Calorie Rule,” The New York Times, October 25, 2007, http://www.nytimes.com/2007/10/25/nyregion/25calories.html (accessed October 26, 2007)</ref>


Eating breakfast may reduce weight gain by adolescents<ref name="pmid18310183">{{cite journal |author=Timlin MT, Pereira MA, Story M, Neumark-Sztainer D |title=Breakfast eating and weight change in a 5-year prospective analysis of adolescents: Project EAT (Eating Among Teens) |journal=Pediatrics |volume=121 |issue=3 |pages=e638-45 |year=2008 |pmid=18310183 |doi=10.1542/peds.2007-1035 |url=http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&pmid=18310183}}</ref>
Eating breakfast may reduce weight gain by adolescents<ref name="pmid18310183">{{cite journal |author=Timlin MT ''et al.'' |title=Breakfast eating and weight change in a 5-year prospective analysis of adolescents: Project EAT (Eating Among Teens) |journal=Pediatrics |volume=121 |pages=e638-45 |year=2008 |pmid=18310183 |url=http://pediatrics.aappublications.org/cgi/pmidlookup?view=long&pmid=18310183}}</ref>


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}[[Category:Suggestion Bot Tag]]
 
[[Category:CZ Live]] [[Category:Health Sciences Workgroup]]

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Obesity is the medical condition associated with excessive stores of body fat, to the extent that it causes serious health risks. Physical problems include high blood pressure, heart disease, some cancers and Diabetes mellitus type 2; emotional problems include low self esteem, and depression. More than a billion people are classed as obese worldwide, and by 2025, 300 million people are expected to suffer from obesity-related diabetes.

There are many ways of measuring body fat, but the most common measures the relationship between weight and height by the body mass index (BMI). A BMI of 30 or more puts you in the category of obese. This method is simple, but imprecise; people with well-developed muscle may have a high BMI yet a low proportion of body fat.

Prevalence and epidemiology

Obesity is increasing in Europe.[1] In the U.S.A., obesity is increased through 2004[2] but has been stable since[3]. Among immigrants, the incidence of obesity increases with the duration of living in the U.S.A..[4]

Causes/etiology

See Genetics of obesity

The proximate cause of obesity is a mix of environmental and genetic factors.[5][6] In only very few cases can obesity in humans be attributed to a single gene defect, but many genes have been found that have (usually rare) variants associated with an increased risk of obesity.

Obesity is generally associated with a state of leptin resistance, that is analogous to the insulin resistance seen in diabetes mellitus type 2 . Leptin is a hormone that is secreted into the blood from fat tissues (adipocytes); it acts on the appetite-regulating centres of the hypothalamus to suppress appetite, and it is secreted at high levels in most obese individuals. However, in these obese individuals, the hypothalamus does not respond appropriately to leptin.

The role of fetal programming,[7] [8][9] perhaps operative in the higher risk of obesity in offspring of older and/or very lean women.

Environment and lifestyle

The increase in overweight and obesity that has taken place during the 20th century is likely to be due to environmental changes (in the widest sense), including especially lifestyle changes that affect diet and exercise habits. While a sedentary lifestyle is involved in the development of a wide range of physical and mental ills, and obesity is associated with a more sedentary lifestyle, it is not obvious that lack of exercise is a major factor in the present obesity epidemic. In a 5.6 years follow-up study of 393 middle-aged healthy subjects, Cambridge epidemiologists demonstrated that carrying excess weight predicted a sedentary lifestyle, but that sedentary time did not predict weight gain.[10] Failure of sedentary time to predict weight gain might conceivably reflect insufficient sample size to reveal a significant prediction, as might greater errors in estimating sedentary time than measuring weight change.

Many other changes in environment and lifestyle may be involved in the increasing prevalence of obesity. In one multi-center review of the literature, 10 other factors, including epigenetic changes were found to be equally plausible etiologic factors contributing to the epidemic.[11][12] Stress and depression (and associated disruptions of sleep) can lead to obesity.[13] [14][11]; changes in eating patterns may contribute[15][16][17] and cultural changes in perceptions of overweight[18] Smoking cessation has a well known effect to increase caloric intake.

  Evolutionary perspectives of obesity

To fully understand the causes and prevalence of obesity, evolutionary factors may need integration into the mix of environmental and genetic proximate causes of obesity. Evolutionary medicine suggests we get fat because of built-in encouragements to eat heartily when we have plenty to eat and to restrict energy expenditures in preparation for inevitable food shortages. It may also suggest we consider the effect of the types of food we eat compared to those evolution adapted us to eat. We’ve only recently, on an evolutionary timescale, begun to eat readily absorbable carbohydrates in disproportionate amounts. Our hunter-gatherer ancestors had little access to such food items, with the exception of a bit of honey. Now we have so-called refined carbohydrates readily available and much consumed. Those include granulated sugar and sucrose dissolved in soft drinks; syrups and candies; milled cereal grain flours and their host pastries, pastas and breads; and many other processed ‘high glycemic’ foods. Those foods stimulate the secretion of insulin as control for glucose homeostasis, and induce other hormonal changes that influence appetite and efficiency of energy utilization. Science writer Gary Taubes summarizes the argument:

“There is considerable evidence that the obesity epidemic is caused by a hormonal phenomenon, specifically by the consumption of refined carbohydrates, starches and sugars, all of which prompt (sooner or later) excessive insulin secretion. Insulin is the primary regulator of fat storage. When insulin levels are elevated, fat accumulates in our body tissue; when they fall, fat is released and we use it for fuel. By stimulating insulin secretion, carbohydrates make us fat; by driving us to accumulate fat, they increase hunger and decrease the energy we expend in metabolism and physical activity. In short, obesity is caused not by overeating or sedentary behaviour, but by hormonal malfunctioning triggered by the consumption of particular types of carbohydrate-containing foods.”[19]

Pathophysiology

The response to a meal in obesity: the insulin paradox

All consumers of refined starches, soft drinks, high-fructose corn syrups and other energy-replete products are not born equal. Obese persons, after a meal, appear to burn carbohydrates less efficiently and fat even more poorly.[20] A contribution of leptin resistance was suggested, as circulating concentrations of leptin were higher in the obese men that were the least efficient metabolisers of fat. However, the arrow of causality may be oriented in the other direction. In persons with a family history of obesity, the earliest obesogenic changes are not related to leptin, but to metabolic efficiency and to insulin status and responsiveness: subjects at increased risk of obesity oxidize carbohydrates more quickly and fat more slowly, and have lower insulin, consistent with a greater insulin sensitivity.[21] These findings contrast with those implicating obesity with the development, over the long term, of the opposite of insulin sensitivity, i.e. insulin resistance.

Magnesium Obese subjects, like type II diabetics, are magnesium deficient.[22] This deficiency is intracellular, and measuring intracellular magnesium requires techniques not yet available in routine clinical settings. Magnesium is required in more than 300 enzymatic reactions, including several that are rate-limiting in carbohydrate utilization. Insulin action depends on magnesium availability in cells and high glucose exposure leads to magnesium depletion and insulin resistance. In obese children, magnesium deficiency precedes insulin resistance[22], but how the heightened responsivity of cells to insulin, that is characteristic of the pre-obese state,[21] relates to magnesium deficiency is not known.

Oxidative stress and reductant stress

At the scale of the adipocyte, we are facing a paradox similar to the one involving insulin. Obesity may present associated with a range of abnormalities: insulin resistance, chronic inflammation, oxidative stress and a range of ills aggregating in what has been called the metabolic syndrome. It thus appears reasonable to assume that adipocytes, in obesity, are in a state of oxidative stress. However, studying obesity in isolation, it became apparent that obesity at the adipocyte level required the opposite of oxidative stress, e.g. a balance between oxidants and reductants tilted in favour of the latter.[23]

Omega-6 vs. omega-3 unsaturated fatty acids

The amount and type of fat to which adipocytes are exposed conditions their development. The amount of omega-6 fatty acids in the diet, in absolute terms as well as relative to the amounts of omega-3 fatty acids, have risen sharply since 1945 due to novel techniques to extract fat from vegetable sources. Omega-6 fatty acids, as a prostacyclin precursors, enhance cyclic AMP-dependent signaling pathways in preadipocytes and promote the development of mature adipocytes. Only by modulating the proportion of omega-6 fatty acids in the diet (without increasing total caloric intake), it is possible to cause in animals a 50% increase in body mass.[24]


Starving in a sea of plenty

In 2008, a twin study was published which carefully selected, from 2,453 young healthy twin pairs, 14 pairs that were discordant for obesity (one twin being obese, and the other not).[25] This study ruled out all genetic factors, as well as intrauterine influences and several environmental factors commonly shared amongst siblings of similar ages. The most significant changes in adipocytes were a sharp decrease in the number of mitochondria, the power plants of the cells that are involved in fat burning, and a specific decrease in their ability to oxidize (burn) three amino acids called branched-chain amino acids, that are the first amino acids to be used as fuel when other sources are unavailable. These amino acids, being poorly catabolized, were higher in the circulation; this signalled the release of higher amounts of more insulin, possibly leading to a vicious cycle. Considering metabolic pathways that were, on the contrary, up-regulated, the researchers found that numerous inflammatory cascades were overactive. The decline in the number of mitochondria remains the most important finding, which will help to design therapies addressing the fact that, in the disease of affluent civilisations par excellence, adipocytes and their energy-producing organelles, the mitochondria, are "starving in a sea of plenty".

The gut flora of the obese: the enemy within

The gut flora, which fulfills an essential symbiotic role in animal metabolism, is probably the first victim of a high-fat diet. Before one becomes obese due to dietary excesses, the trillions of micro-organisms which inhabit our intestines have already transformed into a pro-inflammatory, obesogenic organ.[26][27][28]

Treatment

See also Bariatric surgery, Drug treatments for obesity and Exercise and body weight

The mainstay of treatment for obesity is an energy-limited diet and increased exercise. In studies, diet and exercise programs have consistently produced an average weight loss of approximately 8% of total body mass (excluding study drop-outs). While not all dieters will be satisfied with this outcome, a loss of as little as 5% of body mass can create large health benefits. A more intractable therapeutic problem appears to be weight loss maintenance. Of dieters who manage to lose 10% or more of their body mass in studies, 80-95% will regain that weight within two to five years, supporting the finding that the body has various mechanisms that maintain weight at a certain set point.

A clinical practice guideline issued by the American College of Physicians in 2005 made five recommendations:[29]

  1. People with a BMI above 30 should be counseled on diet, exercise and other relevant behavioral interventions, and set a realistic goal for weight loss.
  2. If these goals are not achieved, pharmacotherapy can be offered. The patient needs to be informed of the possibility of side-effects and the unavailability of long-term safety and efficacy data.
  3. Drug therapy may consist of sibutramine, orlistat, phentermine, diethylpropion, fluoxetine, and bupropion. For more severe cases of obesity, stronger drugs such as amphetamine and methamphetamine may be used on a selective basis. Evidence is not sufficient to recommend sertraline, topiramate, or zonisamide.
  4. In patients with BMI > 40 who fail to achieve their weight loss goals (with or without medication) and who develop obesity-related complications, referral for bariatric surgery may be indicated. The patient needs to be aware of the potential complications.
  5. Those requiring bariatric surgery should be referred to high-volume referral centers, as the evidence suggests that surgeons who frequently perform these procedures have fewer complications.

A clinical practice guideline by the U.S. Preventive Services Task Force (USPSTF) concluded that the evidence is insufficient to recommend for or against routine behavioral counseling to promote a healthy diet in unselected patients in primary care settings, but that intensive behavioral dietary counseling is recommended in those with hyperlipidemia and other known risk factors for cardiovascular and diet-related chronic disease. Intensive counseling can be delivered by primary care clinicians or by referral to other specialists, such as nutritionists or dietitians.[30][31]

Counseling

A meta-analysis of randomized controlled trials concluded that "compared with usual care, dietary counseling interventions produce modest weight losses that diminish over time."[32]

The role of genetic counseling is unclear[33]; but based on a study done of hypercholesterolemia, it is possible that genetic counseling might lead to patients preferring medication over diet therapy.[34]

Delivery method for counseling

Diets

For more information, see: Diet (weight loss).


Portion control

A randomized controlled trial found that patients using portion control plates and log books had more weight loss and less use of hypoglycemic drugs.[39]

Drink more water

Encouraging more water drinking may help.[40]

Financial incentives

Financial incentives may help.[41]

Food labeling

The Nutrition Labeling and Education Act (NLEA) of 1990 went into effect in 1994 to require labeling on on packaged foods.

New York City required labeling by restaurants with 15 or more outlets to post caloric content starting July, 2008.[42] The New York law may increase awareness of calories.[43][44]

Public Law 111-147, the Patient Protection and Affordable Care Act, mandates that restaurants with 20 or more outlets nationwide post caloric information “in a clear and conspicuous manner.”[42]

Medications

For more information, see: Drug treatments for obesity.


Bariatric surgery

For more information, see: Bariatric surgery.

Bariatric surgery (or "weight loss surgery") is the use of surgical interventions in the treatment of obesity. As every surgical intervention may lead to complications, it is regarded as a last resort when dietary modification and pharmacological treatment have proven to be unsuccessful. In the U.S.A.,Medicare will only only pay for procedures performed at approved facilities.[45]

  • Predominantly restrictive procedures. The most common approaches are reducing the volume of the stomach, producing an earlier sense of satiation (e.g. by adjustable gastric banding and vertical banded gastroplasty).
  • Predominantly malabsorptive procedures Others procedures also reduce the length of bowel that food will be in contact with, directly reducing absorption (gastric bypass surgery).

Band surgery is reversible, while gastric bypass surgery is not. In general, gastric bypass surgery leads to more weight loss than band surgery. A meta-analysis by the American College of Physicians reports the following weight loss at 36 months:[46]

  • Biliopancreatic diversion - 53 kg
  • Roux-en-Y gastric bypass - 41 kg (Open - 42 kg; Laparoscopic - 38 kg)
  • Adjustable gastric banding - 35 kg
  • Vertical banded gastroplasty - 32 kg

This analysis does not include a more recent randomized controlled trial.[47]

Two studies report decreases in mortality from bariatric surgery.[48][49] In the Swedish randomized controlled trial, patients with a BMI of 34 or more for men and 38 or more for women underwent various types of bariatric surgery and were followed for a mean of 11 years. Surgery patients had 5% mortality while control patients had 6.3% mortality. [48] In a Utah retrospective cohort study that followed patients for a mean of 7 years after various types of gastric bypass, surgery patients had 0.4% mortality while control patients had 0.6% mortality.[49]

Bariatric surgery remits diabetes mellitus type 2 in more than 1 of every two people after 2 years if they are similar to the patients in the randomized controlled trial by Dixon et al..[50] In this trial, 73% of the patients remitted their diabetes versus 13% of the patients in the control group.

Prevention

Display of calorie information on the menus or menu boards of restaurants has been proposed by the city of New York.[51]

Eating breakfast may reduce weight gain by adolescents[52]

References

  1. ↑ Kotseva K et al. (2009). "Cardiovascular prevention guidelines in daily practice: a comparison of EUROASPIRE I, II, and III surveys in eight European countries". Lancet 373: 929–40. PMID 19286092.
  2. ↑ Ogden CL et al. (2006). "Prevalence of overweight and obesity in the United States, 1999-2004". JAMA 295: 1549–55. PMID 16595758.
  3. ↑ Ogden CL et al. (2008). "High body mass index for age among US children and adolescents, 2003-2006". JAMA 299: 2401–5. PMID 18505949.
  4. ↑ Goel MS et al. (2004). "Obesity among US immigrant subgroups by duration of residence". JAMA 292: 2860–7. PMID 15598917.
  5. ↑ Stunkard AJ et al. (1990). "The body-mass index of twins who have been reared apart". N Eng J Med 322: 1483–7. PMID 2336075.
  6. ↑ Christakis NA, Fowler JH (2007). "The spread of obesity in a large social network over 32 years". N Engl J Med 357: 370–9. PMID 17652652.
  7. ↑ Breier BH et al. (2001). "Fetal programming of appetite and obesity". Mol Cell Endocrinol 185: 73-9. PMID 11738796.
  8. ↑ Vickers MH et al. (2001). "Dysregulation of the adipoinsular axis - a mechanism for the pathogenesis of hyperleptinemia and adipogenic diabetes induced by fetal programming". J Endocrinol 170: 323-32. PMID 11479129.
  9. ↑ Vickers MH et al. (2000). "Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition". Am J Physiol 279: E83-7. PMID 10893326.
  10. ↑ Ekelund U et al.(2008) Time spent being sedentary and weight gain in healthy adults: reverse or bidirectional causality? Am J Clin Nutr 88:612-7
  11. ↑ 11.0 11.1 Keith SW et al. (2006). "Putative contributors to the secular increase in obesity: exploring the roads less traveled". Int J Obes 30: 1585–94. PMID 16801930.
  12. ↑ Wansink B, Payne CR (2009). "The joy of cooking too much: 70 years of calorie increases in classic recipes.". Ann Intern Med 150 (4): 291-2. PMID 19221391. [e]
  13. ↑ Kivimäki M et al. (2009). "Common mental disorder and obesity: insight from four repeat measures over 19 years: prospective Whitehall II cohort study". BMJ 339: b3765. PMID 19808765.
  14. ↑ Vgontzas AN et al. (2008). "Short sleep duration and obesity: the role of emotional stress and sleep disturbances". Int J Obes 32: 801-9. PMID 18253159.
  15. ↑ Roger, V. L.; A. S. Go, D. M. Lloyd-Jones, E. J. Benjamin, J. D. Berry, W. B. Borden, D. M. Bravata, S. Dai, E. S. Ford, C. S. Fox, H. J. Fullerton, C. Gillespie, S. M. Hailpern, J. A. Heit, V. J. Howard, B. M. Kissela, S. J. Kittner, D. T. Lackland, J. H. Lichtman, L. D. Lisabeth, D. M. Makuc, G. M. Marcus, A. Marelli, D. B. Matchar, C. S. Moy, D. Mozaffarian, M. E. Mussolino, G. Nichol, N. P. Paynter, E. Z. Soliman, P. D. Sorlie, N. Sotoodehnia, T. N. Turan, S. S. Virani, N. D. Wong, D. Woo, M. B. Turner, on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee (2011-12-15). "Heart Disease and Stroke Statistics--2012 Update: A Report From the American Heart Association". Circulation. DOI:10.1161/CIR.0b013e31823ac046. ISSN 1524-4539 0009-7322, 1524-4539. Retrieved on 2011-12-16. Research Blogging.
  16. ↑ Duffey KJ, Popkin BM (2011). "Energy density, portion size, and eating occasions: contributions to increased energy intake in the United States, 1977-2006.". PLoS Med 8 (6): e1001050. DOI:10.1371/journal.pmed.1001050. PMID 21738451. PMC PMC3125292. Research Blogging.
  17. ↑ Maruyama, K; et al. (2008-10-21). "The joint impact on being overweight of self reported behaviours of eating quickly and eating until full : cross sectional survey". BMJ 337: a2002.
  18. ↑ Johnson F et al. (2008). "Changing perceptions of weight in Great Britain: comparison of two population surveys". BMJ 337: a494. PMID 18617488.
  19. ↑ Taubes G. (2008) The great diet delusion: It is time for nutrition researchers and health authorities to wake up to the fact that people do not get fat simply because they overeat. New Scientist 19 January 2008, page 17
  20. ↑ Lopes IM et al. (2001). "Effects of leptin resistance on acute fuel metabolism after a high carbohydrate load in lean and overweight young men". J Am Coll Nutr 20: 643–8. PMID 11771681.
  21. ↑ 21.0 21.1 Giacco R et al. (2004). "Insulin sensitivity is increased and fat oxidation after a high-fat meal is reduced in normal-weight healthy men with strong familial predisposition to overweight". Int J Obes Relat Metab Disord 28: 342–8. PMID 14970841.
  22. ↑ 22.0 22.1 Takaya J et al. (2003). "Intracellular magnesium of platelets in children with diabetes and obesity". Metab Clin Exp 52: 468–71. PMID 12701060.
  23. ↑ Galinier A et al. (2006). "Adipose tissue proadipogenic redox changes in obesity". J Biol Chem 281: 12682–7. PMID 16377639.
  24. ↑ Massiera F et al. (2003). "Arachidonic acid and prostacyclin signaling promote adipose tissue development: a human health concern?". J Lipid Res 44: 271–9. PMID 12576509.
  25. ↑ Pietiläinen KH et al. (2008). "Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity". PLoS Med 5: e51. PMID 18336063.
  26. ↑ Kalliomäki M et al. (2008). "Early differences in fecal microbiota composition in children may predict overweight". Am J Clin Nutr 87: 534–8. PMID 18326589.
  27. ↑ Cani PD et al. (2008). "Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice". Diabetes. PMID 18305141.
  28. ↑ Cani PD et al. (2007). "Metabolic endotoxemia initiates obesity and insulin resistance". Diabetes 56: 1761–72. PMID 17456850.
  29. ↑ Snow V et al. (2005). "Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians". Ann Intern Med 142: 525-31. PMID 15809464. [1].
  30. ↑ Behavioral counseling in primary care to promote a healthy diet: recommendations and rationale.. Retrieved on 2007-05-22.
  31. ↑ Pignone MP et al. (2003). "Counseling to promote a healthy diet in adults: a summary of the evidence for the U.S. Preventive Services Task Force". Am J Prev Med 24: 75-92. PMID 12554027.
  32. ↑ Dansinger ML et al. (2007). "Meta-analysis: the effect of dietary counseling for weight loss". Ann Intern Med 147: 41-50. PMID 17606960.
  33. ↑ Marteau T et al. (2004). "Psychological impact of genetic testing for familial hypercholesterolemia within a previously aware population: a randomized controlled trial". Am J Med Genet A 128: 285–93. PMID 15216550.
  34. ↑ Rief W et al. (2007). "Is information on genetic determinants of obesity helpful or harmful for obese people?-A randomized clinical trial". J Gen Intern Med 22: 1553–9. PMID 17879121.
  35. ↑ Svetkey LP, Stevens VJ, Brantley PJ, Appel LJ, Hollis JF, Loria CM et al. (2008). "Comparison of strategies for sustaining weight loss: the weight loss maintenance randomized controlled trial.". JAMA 299 (10): 1139-48. DOI:10.1001/jama.299.10.1139. PMID 18334689. Research Blogging. Review in: Evid Based Med. 2008 Aug;13(4):109 Review in: ACP J Club. 2008 Jul;149(1):4
  36. ↑ Tate DF, Jackvony EH, Wing RR (2003). "Effects of Internet behavioral counseling on weight loss in adults at risk for type 2 diabetes: a randomized trial.". JAMA 289 (14): 1833-6. DOI:10.1001/jama.289.14.1833. PMID 12684363. Research Blogging.
  37. ↑ Hunter CM et al. (2008). "Weight management using the internet a randomized controlled trial". Am J Prev Med 34: 119–26. PMID 18201641.
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  39. ↑ Pedersen SD et al. (2007). "Portion control plate for weight loss in obese patients with type 2 diabetes mellitus: a controlled clinical trial". Arch Intern Med 167: 1277–83. PMID 17592101. ACP Journal Club review
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  41. ↑ Volpp KG et al. (2008). "Financial incentive-based approaches for weight loss: a randomized trial". JAMA 300: 2631–7. PMID 19066383.
  42. ↑ 42.0 42.1 Nestle M (2010). "Health care reform in action--calorie labeling goes national.". N Engl J Med 362 (25): 2343-5. DOI:10.1056/NEJMp1003814. PMID 20375399. Research Blogging.
  43. ↑ Elbel B, Kersh R, Brescoll VL, Dixon LB (2009). "Calorie labeling and food choices: a first look at the effects on low-income people in New York City.". Health Aff (Millwood) 28 (6): w1110-21. DOI:10.1377/hlthaff.28.6.w1110. PMID 19808705. Research Blogging.
  44. ↑ Dumanovsky T, Huang CY, Bassett MT, Silver LD (2010). "Consumer awareness of fast-food calorie information in New York City after implementation of a menu labeling regulation.". Am J Public Health 100 (12): 2520-5. DOI:10.2105/AJPH.2010.191908. PMID 20966367. Research Blogging.
  45. ↑ Bariatric Surgery. Centers for Medicare & Medicaid Services. Retrieved on 2008-06-26.
  46. ↑ Maggard MA et al. (2005). "Meta-analysis: surgical treatment of obesity". Ann Intern Med 142: 547–59. PMID 15809466.
  47. ↑ Nguyen NT et al. (2009)A prospective randomized trial of laparoscopic gastric bypass versus laparoscopic adjustable gastric banding for the treatment of morbid obesity: Outcomes, quality of life, and costs Ann Surg 250:631-41}}
  48. ↑ 48.0 48.1 Sjöström L et al. (2007). "Effects of bariatric surgery on mortality in Swedish obese subjects". N Engl J Med 357: 741-52. DOI:10.1056/NEJMoa066254. PMID 17715408. Research Blogging.
  49. ↑ 49.0 49.1 Adams TD et al. (2007). "Long-term mortality after gastric bypass surgery". N Engl J Med 357: 753-61. PMID 17715409.
  50. ↑ Dixon JB et al. (2008). "Adjustable gastric banding and conventional therapy for type 2 diabetes: a randomized controlled trial". JAMA 299: 316–23. PMID 18212316.
  51. ↑ Rivera R (2007) “New York City Reintroduces Calorie Rule,” The New York Times, October 25, 2007, http://www.nytimes.com/2007/10/25/nyregion/25calories.html (accessed October 26, 2007)
  52. ↑ Timlin MT et al. (2008). "Breakfast eating and weight change in a 5-year prospective analysis of adolescents: Project EAT (Eating Among Teens)". Pediatrics 121: e638-45. PMID 18310183.
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