The dramatic increase in obesity within one or two generations cannot possibly be due to a change in genetics. It is the processing, distribution, and availability of foods that have changed, not the brain. For most people, in the presence of pleasant tasting (high calorie) foods, the brain’s reward circuitry overwhelms the satiety signals. For 2 million years, overeating (on the occasional basis when that was possible) had adaptive value, and it has only been since the rise of an omnipresent obesogenic environment that such behavior has become maladaptive, resulting in widespread obesity. Long-term weight loss is, at minimum, a two-part process: (1) initial weight loss and (2) relapse prevention. All weight loss programs (diet, pharmacology, or surgical) work in the short run, but none used alone have proven widely effective in the long term. After initial weight loss, relapse is common because until recently interventions failed to consider our evolutionary history and thus have underestimated the sensory/reward aspects of feeding behavior. Strongly heritable behavioral characteristics that differentiate obesity-prone individuals from others (e.g., food cue responsiveness, satiety responsiveness) have now been identified and can potentially be targeted to help people learn how to better interact with an obesogenic environment.
- brain satiety mechanisms
- evolutionary pressures
- heritable traits
- obesogenic environment
1. Introduction: The brain and regulation of food intake
Up until at least 1973, the brain was believed to act much like a thermostat in its regulation of food intake and body weight. Hundreds of studies had shown that damage to the ventromedial hypothalamus (VMH) resulted in hyperphagia and obesity in a wide variety of species including humans and that lesions of the adjacent lateral hypothalamus (LH) resulted in aphagia and weight loss . Female rats with large VMH lesions frequently doubled their body weight within 30 days . In 1954, Eliot Stellar used these two nuclei as the model example for his dual-center hypothesis for motivated behavior . The LH was the “excitatory center,” activation of which caused the organism to eat. Food intake provided some (unknown at that time) manner of glucostatic, lipostatic, and/or thermostatic feedback to the VMH, the “inhibitory center,” which then inhibited the LH, resulting in cessation of feeding. The underlying principal was homeostasis, i.e., food intake decreased when body weight exceeded some stable state (set point) and increased when body weight fell below this set point (see  for a history of set point theory). The weight changes observed after lesions were generally attributed to a resetting of the set point .
So compelling was the evidence, and model, that the leading researchers of human obesity of that era directly compared obese humans to obese rats with VMH lesions [6–8]. Similarities in patterns of food intake, hyperreactivity to the sensory qualities of food (e.g., taste), and unwillingness to work for food were particularly noted. Researchers concluded that obese individuals had “a weak ventromedial hypothalamus” [6, p. 450] and that “the obesity of rats and men has a common physiological locus in the ventromedial hypothalamus” [8, p. 143].
The simplicity of the dual-center model was abandoned in the 1970s when, first, it was found that transection of the ventral noradrenergic bundle at the level of the midbrain resulted in overeating and obesity  and, second, when a few years later it was discovered that lesions of the hypothalamic paraventricular nucleus (PVN) also produced hyperphagia and obesity [10, 11]. The next 30 years of research (with lab rats) focused on the role of the PVN and arcuate nuclei  and circulating levels of leptin and insulin, hormones that are released in proportion to body fat content . Mice that have mutations in the gene for leptin (ob/ob) become markedly obese . Other brain structures were also found to play a role in the regulation of food intake and body weight, including the posterodorsal amygdala [15, 16]. The model had become more complex, but the underlying principal was still believed to be energy homeostasis [13, 17] and the related concept of set point (or settling point). Human obesity was explained, at least in part, as a malfunction of the system, e.g., resistance to leptin .
The studies with rats confined in small cages and fed a single standard lab chow diet have contributed greatly to our understanding of brain mechanisms regulating individual meal parameters , but how well do they explain regulation of body weight in free-living humans? The answer is not very well. Similar to lab rats, humans do not overeat when offered a bland diet ad libitum , but many researchers have noted that homeostatic controls appear to be absent in environments with an abundance of good-tasting foods [13, 18, 21–26]. In fact, in a long series of studies, de Castro and colleagues determined that only 14% of the variance in the daily food intake of free-living humans could be explained by brain homeostatic mechanisms . As stated by Cameron and Doucet , “…when given a barrage of anorexigenic signals, humans still manage to overconsume even at gluttonous levels” (p. 183).
The prevalence of overweight and obese individuals in the United States has nearly tripled since 1980 . One third of adults are overweight (BMI > 25 kg/m2), and over one third more are clinically obese (BMI > 30 kg/m2) . Researchers have projected that at least 42–44% of Americans will be obese by 2030 [29, 30]. This is a substantial increase since 1960 when only about one in five Americans was overweight . Any explanation for the regulation of body weight in humans must be able to account for this dramatic increase in obesity in just a few-decade time. It is highly unlikely that the modern obesity pandemic is due to recent pathology in genetics, metabolism, or the brain homeostatic (inhibitory) controls of feeding behavior . Two thirds of the American population could not suddenly have become leptin resistant.
In actuality, the brain is reacting to present-day environmental stimuli exactly in the manner in which it evolved during 2 million years of environmental selective pressures since the appearance of the genus
One thing is certain: the brain’s reward circuitry is not homeostatic, i.e., there is no upper-level body weight set point at which it shuts down . In short, the brain developed as an organ attracted to energy-dense rewards. For many people, the sensory/reward aspects of food simply overwhelm the homeostatic satiety signals [18, 23].
2. The environment and obesity
Until about 8000 BC, all humans lived in small nomadic, hunter-gatherer tribes [42, 43]. King  has reviewed the anthropological research showing that for the previous 2 million years, there were certainly periods (short and/or prolonged) of food shortages. It would have been advantageous to store energy as fat to survive periods of deprivation and have energy to hunt and thus, when food was plentiful, to consume more calories than was required just to satisfy short-term inter-meal deficits in energy [21, 25, 44]. In a restricted environment, this would have resulted, at most, in a moderately overweight phenotype.
In short, the modern societal practice of “three meals plus snacks every day is abnormal from an evolutionary perspective” [45, p. 16,647]. Interestingly, recent research has shown that intermittent fasting not only reduces body weight [45–48] but improves clinical health indicators [45, 47, 48] and may reduce processes leading to diseases such as diabetes, heart disease, and certain cancers [45, 47].
What has changed is not the brain, but the environment [23, 26]. The anthropological record reveals that the switch from hunting-gathering to farming as the primary source of food (with a greater reliance on carbohydrates than lean meat) began 10,000 years ago [49, 50]. The use of salt (and probably herbs and spices) to flavor foods dates back to at least the Bronze Age , but sugar was not widely available until the 1500s . However, it was the industrialization of the food supply (i.e., the processing and distribution of food) in the last half of the twentieth century that has had the most dramatic impact on how today’s humans eat [26, 53, 54].
The availability of high-calorie foods (e.g., carbohydrates and fats) has markedly increased in the United States since the 1970s . One of the most obvious changes that began in the 1970s, at about the same time as the prevalence of obesity began to rapidly increase, was the proliferation of fast-food restaurants. McDonald’s opened in 1955, had 1000 restaurants in 1968, and today has over 36,000 restaurants in over 100 countries. Burger King opened in 1954, had 275 restaurants in 1967, and today has 13,000 restaurants in 79 countries. Wendy’s opened in 1969 and today has over 6850 restaurants. Similarly, today, Kentucky Fried Chicken has over 19,400 restaurants, Pizza Hut over 11,000, Taco Bell over 6500, Arby’s over 3300, Chick-fil-A over 1950, and Church’s Chicken nearly 1700 restaurants. Most of them have drive-up windows. Altogether, sales at the US fast-food restaurants increased from $16.2 billion in 1975 to about $110 billion by 2004  with a corresponding increase in American’s proportional consumption of calories in the form sweetened drinks and such foods as cheeseburgers and pizza [57, 58]. Add to fast-food restaurants an increase in cafeteria and full-menu restaurants, convenience stores, and dispensing machines, and the end result is an obesogenic environment: a high density of high-calorie food sources that require little energy expenditure for consumers to access.
Numerous studies have found a positive association between the geographical density of fast-food restaurants and prevalence of obesity [59–64] or obesity and the frequency with which individuals eat at restaurants [65–70; see also 71]. Compared to normal-weight persons, overweight and obese individuals consume larger meals when eating away from home . Many studies have also found that when groups of people move from areas of the world where the prevalence of obesity is low to an obesogenic environment (e.g., the United States), they gain weight and eventually display the same prevalence of obesity as is found among those who were born in the obesogenic environment [73; see 24 for a review]. Freshman students often gain excess weight during the first few weeks of attending college . One third of American adults may not (yet) be overweight, but many of them live in areas (e.g., very rural) that are not obesogenic.
As with any genetic trait (e.g., height), there is diversity, and some people are more obesity prone than others [18, 75–77]. Obese individuals are less responsive to homeostatic satiety mechanisms [76–78] and are much more responsive to external feeding stimuli than are normal-weight people [7, 24, 27, 77, 79]. The latter includes not only the taste and texture of food but also social cues (e.g., number of others eating, the sight of and variety of foods, portion size, time of day). Compared to others, obese individuals have a strong tendency to discount delayed food rewards in favor of immediate rewards [80–83].
Studies with twins reveal that appetite (responsiveness to food cues) and satiety responsiveness are highly heritable behavioral characteristics [27, 76, 77, 79], as is cognitive restraint, which is generally less for obese individuals [27, 84, 85]. These heritable behavioral characteristics emerge early in life , and while they do not cause obesity directly, they result in individuals being more susceptible to overeating in an obesogenic environment [18, 77, 86]. Not everyone has these heritable traits, but based on the obesity statistics, a large majority of humans do have them. At present, at least 32 genetic loci associated with BMI have been identified .
In summary, obesity is the result of interaction between genetic risks and the environment. The brain reward circuitry that evolved during 2 million years of our hunter-gatherer ancestry has resulted in many humans being more responsive to environmental food stimuli than they are to caloric/homeostatic stimuli [7, 21, 23, 24, 27, 75–77]. In the words of one group of researchers, humans have “fat brains [and] greedy genes” .
3. Interventions to reduce obesity
As the prevalence of obesity has increased, the number and variety of weight loss programs have increased almost exponentially. Using the key terms “obesity,” “humans,” and “weight loss,” Medline indicates 67 publications in the time period 1965–1974 and 13,904 publications from 2006 to 2015. Today, Americans spend over $60 billion a year on attempts to lose weight . The medical cost of treating adult obesity in the United States is between $147 and $210 billion per year .
All diets work—in the short run. They may differ in the types of food recommended to eat, but when fewer calories are consumed than expended, the result is weight loss. Most overweight and obese individuals have successfully dieted for a few weeks and many for a few months, but in the long run, the success rate of behavioral therapies alone has proven to be very modest at best. Most dieting individuals do not maintain their weight loss [89, 90]. This was first noted nearly 60 years ago:
“Most obese patients will not remain in treatment. Of those who do remain in treatment, most will not lose significant poundage, and of those who do lose weight, most would regain it promptly” [91, p. 87].
Results with pharmacologic treatment of obesity alone have proven equally disappointing [92–94]—individuals achieve meaningful weight loss only when the medication is accompanied by additional lifestyle interventions  and maintain the weight loss (usually modest) only as long as they remain on the drugs . Mean excess weight loss for extremely obese individuals who have undergone bariatric surgery is only about 50% (; see [98, 99] for reviews), with many others losing substantially less weight (see  for a review), and still others eventually regaining much of their excess weight . (Note: the author is not underestimating the health benefits of a 50% loss of excess weight.)
Long-term weight loss is, at minimum, a two-part process: (1) initial weight loss and (2) relapse prevention. The relapse rate is high because it is normal for the evolved brain’s reward circuitry to direct humans to overeat when good-tasting/high-calorie foods are available . Regardless of how weight loss is initially achieved (diet, pharmacology, and/or surgical intervention), sending the client back into an omnipresent obesogenic environment with a few behavioral-cognitive instructions (e.g., counting calories; monitoring carbohydrates, fats, and portion size; eating slowly; more exercise) has not worked long term for most people [89–91, 101].
For many individuals who have recently lost weight, relapse prevention will mean, in part, learning how to reduce food cue responsiveness . Obese individuals are more easily tempted by pleasant-tasting food when it is easily available than are lean individuals , an aspect of the greater responsiveness to external stimuli. Today, the obesogenic environment is omnipresent—in the workplace, in schools, throughout the community, and in the media. Weight-loss interventions have failed because, historically, they have put the responsibility almost exclusively on the individual. In 2012, the Institute of Medicine  concluded that government, industry, the community, the media, and medicine must be part of a multifaceted approach (e.g., an increase in social marketing, as was done with smoking) to help individuals address how to limit and deal with an ever-increasing obesogenic environment [22, 26, 88, 103–105].
In free-living humans living in an obesogenic environment, there is little evidence in support of an upper limit set point around which body weight is regulated in a homeostatic fashion. For most people, the brain’s reward circuitry plays the dominant role in feeding behavior. Living in a restricted environment with periods of food deprivation, it was necessary for survival for
King BM. The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiology & Behavior. 2006; 87: 221-244. DOI: 10.1016/j.physbeh.2005.10.007
King BM., Gaston MG. Reappearance of dynamic hyperphagia during the static phase in medial hypothalamic lesioned rats. Physiology & Behavior. 1977; 18: 945-950. DOI: 10:1016/0031-9384(77)90205-0
Stellar E. The physiology of motivation. Psychological Review. 1954; 61: 5-22. DOI: 10.1037/h0060347
Berridge KC. Motivation concepts in behavioral neuroscience. Physiology & Behavior. 2004; 81: 179-209. DOI: 10.1016/j.physbeh.2004.02.004
Hoebel BG, Teitelbaum P. Weight regulation in normal and hypothalamic hyperphagic rats. Journal of Comparative and Physiological Psychology. 1966; 61: 189-193. DOI: 10.1037/h0023126
Nisbett RE. Hunger, obesity, and the ventromedial hypothalamus. Psychological Review. 1972; 79: 433-453. DOI: 10.1037/h0033519
Schachter S. Obesity and eating. Science. 1968; 161: 751-756. DOI: 10.1126/science.161.3843.751
Schachter S. Some extraordinary facts about obese humans and rats. American Psychologist. 1971; 26: 129-144. DOI: 10.1037/h0030817
Ahlskog JE, Hoebel BG. Overeating and obesity from damage to a noradrenergic system in the brain. Science. 1973; 182: 166-169. DOI: 10.1126/science.182.4108.166
Aravich PF, Sclafani A. Paraventricular hypothalamic lesions and medial hypothalamic knife cuts produce similar hyperphagia syndromes. Behavioral Neuroscience. 1983; 97: 970-983. DOI: 10.1037/0735-7044.97.6.970
Leibowitz SF, Hammer NJ, Chang K. Hypothalamic paraventricular nucleus lesions produce overeating and obesity in the rat. Physiology & Behavior. 1981; 27: 1031-1040. DOI: 10.1016/0031-9384(81)90366-8
Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin, DG. Central nervous system control of food intake. Nature. 2000; 404: 661-671. DOI: 10.1038/35007534
Könner AC, Klöckener T, Brüning JC. Control of energy homeostasis by insulin and leptin: Targeting the arcuate nucleus and beyond. Physiology & Behavior. 2009; 97: 632-638. DOI: 10.1016/j.physbeh.2009.03.027
Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994; 372: 425-432. DOI: 10.1038/372425a0
King BM. Amygdaloid lesion-induced obesity: Relation to sexual behavior, olfaction, and the ventromedial hypothalamus. American Journal of Physiology. 2006; 291: R1201-R1214. DOI: 10.1152/ajpregu.00199.2006
King BM, Kass JM, Cadieux NL, Sam H, Neville KL, Arceneaux ER. Hyperphagia and obesity in female rats with temporal lobe lesions. Physiology & Behavior. 1993; 54: 759-765. DOI: 10.1016/0031-9384(93)90088-W
Woods SC. Signals that influence food intake and body weight. Physiology & Behavior. 2005; 86: 709-716. DOI: 10.1016/j.physbeh.2005.08.060
Levin BE. Factors promoting and ameliorating the development of obesity. Physiology & Behavior. 2005; 86: 633-639. DOI: 10.1016/j.physbeh.2005.08.054
de Graaf C, Blom WAM, Smeets PAM, Stafleu A, Hendriks HFJ. Biomarkers of satiation and satiety. American Journal of Clinical Nutrition. 2004; 79: 946-961.
Cabanac M, Rabe EF. Influence of a monotonous food on body weight regulation in humans. Physiology & Behavior. 1976; 17: 675-678. DOI: 10.1016/0031-9384(76)90168-2
Cameron J, Doucet É. Getting to the bottom of feeding behavior: Who’s on top? Applied Physiology, Nutrition, and Metabolism. 2007; 32: 177-189. DOI: 10.1139/H06-072
Egger G, Swinburn B. An “ecological” approach to the obesity pandemic. British Medical Journal. 1997; 315: 477. DOI: 10.1136/bmj.315.7106.477
King BM. The modern obesity epidemic, ancestral hunter-gatherers, and the sensory/reward control of food intake. American Psychologist. 2013; 68: 88-96. DOI: 10.1037/a0030684
Levitsky DA. The non-regulation of food intake in humans: Hope for reversing the epidemic of obesity. Physiology & Behavior. 2005; 86: 623-632. DOI: 10.1016/j.physbeh.2005.08.053
Pinel JPJ, Assanand S, Lehman DR. Hunger, eating, and ill health. American Psychologist. 2000; 55: 1105-1116. DOI: 10.1037/0003-066X.55.10.1105
Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, et al. The global obesity pandemic: Shaped by global drivers and local environments. Lancet. 2011; 378: 804-814. DOI: 10.1016/S0140-6736(11)60813-1
de Castro JM. The control of food intake of free-living humans: Putting the pieces back together. Physiology & Behavior. 2010; 100: 446-453. DOI: 10.1016/j.physbeh.2010.04.028
Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. Journal of the American Medical Association. 2014; 311: 806-814. DOI: 10.1001/jama.2014.732
Finkelstein EA, Khavjou OA, Thompson H, Trogdon JG, Pan L, Sherry B, et al. Obesity and severe obesity forecasts through 2030. American Journal of Preventive Medicine. 2012; 42: 563-570. DOI: 10.1016/j.amepre.2011.10.02
TFAH Release. F as in fat: How obesity threatens America’s future 2012. Trust for America’s Health and the Robert Wood Johnson Foundation. 2012. Available from: http://www.healthyamericans.org/report/100/ [Accessed: 2016-05-11]
U.S. Public Health Service. Obesity and Health. (Publication No. 1485). Washington, DC: U.S. Department of Health, Education and Welfare. 1966.
Gautier J-F, Chen K, Salbe AD, Bandy D, Pratley RE, Heiman M, et al. Differential brain responses to satiation in obese and lean men. Diabetes. 2000; 49: 838-846. DOI: 10.2337/diabetes.49.5.838
Liu Y, Gao JH, Liu HL, Fox PT. The temporal response of the brain after eating revealed by functional MRI. Nature. 2000; 405: 1058-1062. DOI: 10.1038/35016590
Matsuda M, Liu Y, Mahankali S, Pu Y, Mahankali A, Wang J, et al. Altered hypothalamic function in response to glucose injection in obese humans. Diabetes. 1999; 48: 1801-1806. DOI: 10.2337/diabetes.48.9.1801
Brooks SJ, Cedernaes J, Schiöth HB. Increased prefrontal and parahippocampal activation with reduced dorsolateral prefrontal and insular cortex activation to food images in obesity: A meta-analysis of fMRI studies. Plos One. 2013; 8(4): e60393. DOI: 10.1371/journal.pone.0060393
Carnell S, Gibson C, Benson L, Ochner CN, Geliebter A. Neuroimaging and obesity: Current knowledge and future directions. Obesity Reviews. 2012; 13: 43-56. DOI: 10.1111/j.1467-789X.2011.00927.x
Stice E, Figlewicz DP, Gosnell BA, Levine AS, Pratt WE. The contribution of brain reward circuits to the obesity epidemic. Neuroscience and Biobehavioral Reviews. 2013; 37: 2047-2058. DOI: 10.1016/j.neubiorev.2012.12.001
Stice E, Yokum S, Bohon C, Marti N, Smolen A. Reward circuitry responsivity to food predicts future increases in body mass: Moderating effects of DRD2 and DRD4. Neuroimage. 2010; 50: 1618-1625. DOI: 10.1016/j.neuroimage.2010.01.081
Stice E, Yokum S, Burger KS, Epstein LH, Small DM. Youth at risk for obesity show greater activation of striatal and somatosensory regions to food. Journal of Neuroscience. 2011; 31: 4360-4366. DOI: 10.1523/JNEUROSCI.6604-10.2011
DelParigi A, Chen K, Salbe AD, Hill JO, Wing RR, Reiman EM, et al. Persistence of abnormal neural responses to a meal in postobese individuals. International Journal of Obesity and Related Metabolic Disorders. 2004; 28: 370-377. DOI: 10.1038/sj.ijo.0802558
Zhang Y, von Deneen KM, Tian J, Gold MS, Liu Y. Food addiction and neuroimaging. Current Pharmaceutical Design. 2011; 17: 1149-1157. DOI: 10.2174/138161211795656855
Devore I. Diet and hunter-gatherers. Anthroquest. 1984; 30: 3-5.
Lee RB, Devore I. Problems in the study of hunters and gatherers. In: Lee RB, Devore I, editors. Man the Hunter. Chicago, IL: Aldine; 1968. p. 3-12.
Neel JV. Diabetes mellitus: A “thrifty” genotype rendered detrimental by “progress”? American Journal of Human Genetics. 1962; 14: 353-362.
Mattson MP, Allison DB, Fontana L, Harvie M, Longo VD, Malaisse WJ, et al. Meal frequency and timing in health and disease. Proceedings of the National Academy of Sciences. 2014; 111: 16647-16653. DOI: 10.1073/pnas.1413965111
Horne BD, Muhlestein JB, Anderson, JL. Health effects of intermittent fasting: Hormesis or harm? A systematic review. American Journal of Clinical Nutrition. 2015; 102: 464-470. DOI: 10.3945/ajcn.115.109553
Patterson RE, Laughlin GA, LaCroix AZ, Hartman SJ, Natarajan L, Senger CM, et al. Intermittent fasting and human metabolic health. Journal of the Academy of Nutrition and Dietetics. 2015; 115: 1203-1212. DOI: 10.1016/j.jand.2015.02.018
Tinsley GM, La Bounty PM. Effects of intermittent fasting on body composition and clinical health markers in humans. Nutrition Reviews. 2015; 73: 661-674. DOI: 10.1093/nutrit/nuv041
Cohen MN. Introduction: Rethinking the origins of agriculture. Current Anthropology. 2009; 50: 591-595. DOI: 10.1086/603548
Lichtenstein AH. Dietary fat: A history. Nutrition Reviews. 1999; 57: 11-14. DOI: 10.1111/j.1753-4887.1999.tb01770.x
Outram AK. Hunter-gatherers and the first farmers: The evolution of taste in prehistory. In: Freedman P, editor. Food: The History of Taste. Volume 21. Berkeley, CA: University of California Press; 2007. p. 34-61.
Armelagos GJ. The omnivore’s dilemma: The evolution of the brain and the determinants of food choice. Journal of Anthropological Research. 2010; 66: 161-186. DOI: 10.3998/jar.0521004.0066.201
Grey MA. The industrial food stream and its alternatives in the United States: An introduction. Human Organization. 2000; 59: 143-150. DOI: 10.17730/humo.59.2.xm3235743p6618j3
Popkin BM, Duffey K, Gordon-Larse P. Environmental influences on food choice, physical activity and energy balance. Physiology & Behavior. 2005; 86: 603-613. DOI: 10.1016/j.physbeh.2005.08.051
Putnam J, Allshouse J, Kantor LS. US per capita food supply trends: More calories, refined carbohydrates, and fats. Food Reviews. 2002; 25: 2-15.
Technomic, Inc. Technomic Foodservice Segment Time Series: Limited Service Restaurants (1975-2005). Chicago, IL: Technomic, Inc.; 2004.
Briefel RR, Johnson CL. Secular trends in dietary intake in the United States. Annual Review of Nutrition. 2004; 24: 401-431. DOI: 10.1146/annurev.nutr.23.011702.073349
Nielsen SJ, Popkin BM. Changes in beverage intake between 1977 and 2001. American Journal of Preventive Medicine. 2004; 27: 205-210. DOI: 10.1016/j.amepre.2004.05.005
Fraser LK, Edwards KL. The association between the geography of fast food outlets and childhood obesity rates in Leeds, UK. Health & Place. 2010; 16: 1124-1128. DOI: 10.1016/j.healthplace.2010.07.003
Inagami S, Cohen DA, Brown AF, Asch SM. Body mass index, neighborhood fast food and restaurant concentration, and car ownership. Journal of Urban Health. 2009; 86: 683-695. DOI: 10.1007/s11524-009-9379-y
Maddock J. The relationship between obesity and the prevalence of fast food restaurants: State-level analysis. American Journal of Health Promotion. 2004; 19: 137-143. DOI: 10.4278/0890-1171-19.2.137
Mehta NK, Chang VW. Weight status and restaurant availability: A multilevel analysis. American Journal of Preventive Medicine. 2008; 34: 127-133. DOI: 10.1016/j.amepre.2007.09.031
Papas MA, Alberg AJ, Ewing R, Helzlsover KJ, Gary TL, Klassen AC. The built environment and obesity. Epidemiologic Reviews. 2007; 29: 129-143. DOI: 10.1093/epirev/mxm009
Spence JC, Cutumisu N, Edwards J, Raine KD, Smoyer-Tomic K. Relation between local food environments and obesity among adults. BMC Public Health. 2009; 9: 192. DOI: 10.1186/1471-2458-9-192
Anderson B, Rafferty AP, Lyon-Callo S, Fussma C, Imes G. Fast-food consumption and obesity among Michigan adults. Preventing Chronic Disease. 2011; 8(4): A71.
Bezerra IN, Curioni C, Sichieri R. Association between eating out of home and body weight. Nutrition Reviews. 2012; 70: 65-79. DOI: 10.1111/j.1753-4887.2011.00459.x
Duffey KJ, Gordon-Larsen P, Jacobs DR, Williams OD, Popkin BM. Differential associations of fast food and restaurant food consumption with 3-y change in body mass index: The coronary artery risk development in young adults study. American Journal of Clinical Nutrition. 2007; 85: 201-208.
Holsten JE. Obesity and the community food environment: A systematic review. Public Health and Nutrition. 2009; 12: 397-405. DOI: 10.1017/S1368980008002267
McCrory MA, Fuss PJ, Hays NP, Vinken AG, Greenberg A, Roberts SB. Overeating in America: Association between restaurant food consumption and body fatness in healthy adult men and women ages 19 to 80. Obesity Research. 1999; 7: 564-571. DOI: 10.1002/j.1550-8528.1999.tb00715.x
Thompson OM, Ballew C, Resnicow K, Must A, Bandini LG, Cyr H, et al. Food purchased away from home as a predictor of change in BMI z-score among girls. International Journal of Obesity and Related Metabolic Disorders. 2004; 28: 282-289. DOI: 10.1038/sj.ijo.0802538
Lachat C, Nago G, Verstraeten R, Roberfroid D, Van Camp J, Kolsteren P. Eating out of home and its association with dietary intake: A systematic review of the evidence. Obesity Reviews. 2012; 13: 329-346. DOI: 10.1111/j.1467-789X.2011.00953x
de Castro JM, King GA, Duarte-Gardea M, Gonzalez-Ayala S, Kooshian CH. Overweight and obese humans overeat away from home. Appetite. 2012; 59: 204-211. DOI: 10.1016/j.appet.2012.04.020
Goel MS, McCarthy EP, Phillips RS, Wee CC. Obesity among US immigrant subgroups by duration of residence. Journal of the American Medical Association. 2004; 292: 2860-2867. DOI: 10.1001/jama.292.23.2860
Levitsky DA, Halbmaier CA, Mrdjenovic G. The freshman weight gain: A model for the study of the epidemic of obesity. International Journal of Obesity and Related Metabolic Disorders. 2004; 28: 1435-1442. DOI: 10.1038/sj.ijo.0802776
Blundell JE, Stubbs RJ, Golding C, Croden F, Alam R, Whybrow S, et al. Resistance and susceptibility to weight gain: Individual variability in response to a high-fat diet. Physiology & Behavior. 2005; 86: 614-622. DOI: 10.1016/j.physbeh.2005.08.052
Carnell S, Haworth CMA, Plomin R, Wardle J. Genetic influence on appetite in children. International Journal of Obesity. 2008; 32: 1468-1473. DOI: 10.1038/ijo.2008.127
Carnell S, Wardle J. Appetite and adiposity in children: Evidence for a behavioral susceptibility theory of obesity. American Journal of Clinical Nutrition. 2008; 88: 22-29.
Jansen A, Theunissen N, Slechten K, Nederkoorn C, Boon B, Mulkens S, et al. Overweight children overeat after exposure to food cues. Eating Behaviors. 2003; 4: 197-209. DOI: 10.1016/S1471-0153(03)00011-4
Carnell S, Kim Y, Pryor K. Fat brains, greedy genes, and parent power: A biobehavioural risk model of child and adult obesity. International Review of Psychiatry. 2012; 24: 189-199. DOI: 10.3109/09540261.2012.676988
Bonato DP, Boland FJ. Delay of gratification in obese children. Addictive Behaviors. 1983; 8: 71-74. DOI: 10.1016/0306-4603(83)90059-X
Geller SE, Keane TM, Scheirer CJ. Delay of gratification, locus of control, and eating patterns in obese and nonobese children. Addictive Behaviors. 1981; 6: 9-14. DOI: 10.1016/S0306-4603(81)80002-0
Johnson WG, Parry W, Drabman RS. The performance of obese and normal size children on a delay of gratification task. Addictive Behaviors. 1978; 3: 205-208. DOI: 10.1016/0306-4603(78)90020-5
Weller RE, Cook EW, Avsar KB, Cox JE. Obese women show greater delay discounting than healthy-weight women. Appetite. 2008; 51: 563-569. DOI: 10.1016/j.appet.2008.04.010
de Castro JM. The relationship of cognitive restraint to the spontaneous food and fluid intake of free-living humans. Physiology & Behavior. 1995; 57: 287-295. DOI: 10.1016/0031-9384(94)00229-X
de Castro JM, Lilenfeld L. The influence of heredity on dietary restraint, disinhibition, and perceived hunger in humans. Nutrition. 2005; 21: 446-455. DOI: 10.1016/j.nut.2004.07.010
Maffeis C. Aetiology of overweight and obesity in children and adolescents. European Journal of Pediatrics. 2000; 159: S35-S44. DOI: 10.1007/PL00014361
Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature Genetics. 2010; 42: 937-948. DOI: 10.1038/ng.686
Rodgers GP, Collins FS. The next generation of obesity research. No time to waste. Journal of the American Medical Association. 2012; 308: 1095-1096. DOI: 10.1001/2012.jama.11853
Christiansen T, Bruun JM, Madsen EL, Richelsen B. Weight loss maintenance in severely obese adults after an intensive lifestyle intervention: 2- to 4-year follow-up. Obesity. 2007; 15: 413-420. DOI: 10.1038/oby.2007.530
LeBlanc ES, O’Connor E, Whitlock EP, Patnode CD, Kapka T. Effectiveness of primary care-relevant treatments for obesity in adults: A systematic evidence review for the U.S. Preventive Services Task Force. Annals of Internal Medicine. 2011; 155: 434-447. DOI: 10.7326/0003-4819-155-7-201110040-00006
Cornell Conferences on Therapy. The management of obesity. New York State Journal of Medicine. 1958; 58: 79-87.
Heymsfield SB, Greenberg AS, Fujioka K, Dixon RM, Kushner R, Hunt T, et al. Recombinant leptin for weight loss in obese and lean adults: A randomized, controlled, dose-escalation trial. Journal of the American Medical Association. 1999; 282: 1568-1575. DOI: 10.1001/jama.282.16.1568
Li Z, Maglione M, Tu W, Majica W, Arterburn D, Shugarman LR, et al. Meta-analysis: Pharmacologic treatment of obesity. Annals of Internal Medicine. 2005; 142: 532-546. DOI: 10.7326/0003-4819-142-7-200504050-00012
Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity and overweight: Updated meta-analysis. British Medical Journal. 2007; 335: 1194-1199. DOI: 10.1136/bmj.39385.413113.25
Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity. A systematic and clinical review. Journal of the American Medical Association. 2014; 311: 74-86. DOI: 10.1001/jama.2013.281361
Bray GA, Tartaglia LA. Medicinal strategies in the treatment of obesity. Nature. 2000; 404: 672-677. DOI: 10.1038/35007544
Cobourn C, Chapman MA, Ali A, Amrhein J. Five-year weight loss experience of outpatients receiving laparoscopic adjustable gastric band surgery. Obesity Surgery. 2013; 23: 903-910. DOI: 10.1007/s11695-013-0881-7
O’Brien PE, MacDonald L, Anderson M, Brennan L, Brown WA. Long-term outcomes after bariatric surgery: Fifteen-year follow-up of adjustable gastric banding and a systematic review of the bariatric surgical literature. Annals of Surgery. 2013; 257: 87-94. DOI: 10.1097/SLA.ob013e31827b6c02
Vest AR, Heneghan HM, Agarwal S, Schaver PR, Young JB. Bariatric surgery and cardiovascular outcomes: A systematic review. Heart. 2012; 98: 1763-1777. DOI: 10.1136/heartjnl-2012-301778
Livhits M, Mercado C, Yermilov I, Parikh JA, Dutson E, Mehran A, et al. Preoperative predictors of weight loss following bariatric surgery: Systematic review. Obesity Surgery. 2012; 22: 70-89. DOI: 10.1007/s11695-011-0472-4
Christou NV, Look D, MacLean LD. Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years. Annals of Surgery. 2006; 244: 734-740. DOI: 10.1097/01.sla.0000217592.04061.d5
Institute of Medicine. Accelerating progress in obesity prevention: Solving the weight of the nation. 2012. Available from: http://www.iom.edu/Reports/2012/Accelerating-Progress-in-Obesity-Prevention.aspx [Accessed: 2016-05-11]
Barry CL, Gollust SE, Niederdeppe J. Are Americans ready to solve the weight of the nation? New England Journal of Medicine. 2012; 367: 389-391. DOI: 10.1056/NEJMp1206519
Mitchell NS. Obesity: Overview of an epidemic. Psychiatric Clinics of North America. 2011; 34: 717-732. DOI: 10.1016/j.psc.2011.08.005
Mwanri L, Foley W, Coveney J, Muller R, Verity F, Ward PR, et al. Food supply and the obesity scourge: Is there a relationship? Health. 2012; 4: 1457-1463. DOI: 10.4236/health.2012.412A210