There is a “widespread misimpression” that weight-loss and maintenance for bodies which have become and stayed obese for more than a couple of years, is essentially the same as that for bodies which always have been:
In a commentary published February 26, 2015 in the journal Lancet Diabetes and Endocrinology, four weight-loss specialists set out to correct what they view as the widespread misimpression that people who have become and stayed obese for more than a couple of years can, by diet and exercise alone, return to a normal, healthy weight and stay that way.
"Once obesity is established, however, body weight seems to become biologically 'stamped in' and defended," wrote Mt. Sinai Hospital weight management expert Christopher N. Ochner and colleagues from the medical faculties of the University of Colorado, Northwestern University and the University of Pennsylvania.
“Few individuals ever truly recover from obesity.” Those that do "still have 'obesity in remission,' and are biologically very different from individuals of the same age, sex and body weight who never had obesity." They are constantly at war with their bodies' efforts to return to their highest sustained weight.
That February 2015 commentary together with the August 2013 research article below explain many of the things that I have experienced personally, and that I have personally observed.
An additional article dealing with this issue is located HERE in the DietHobby Archives.
Biological Mechanisms that Promote Weight Regain Following Weight Loss in Obese Humans
by Christopher N. Ochner; Dulce M. Barrios; Clement D. Lee; F. Xavier Pi-Sunyer
Published August 2013
Weight loss dieting remains the treatment of choice for the vast majority of obese individuals, despite the limited long-term success of behavioral weight loss interventions. The reasons for the near universal unsustainability of behavioral weight loss in [formerly] obese individuals have not been fully elucidated, relegating researchers to making educated guesses about how to improve obesity treatment, as opposed to developing interventions targeting the causes of weight regain. This article discusses research on several factors that may contribute to weight regain following weight loss achieved through behavioral interventions, including adipose cellularity, endocrine function, energy metabolism, neural responsivity, and addiction-like neural mechanisms. All of these mechanisms are engaged prior to weight loss, suggesting that so called “anti-starvation” mechanisms are activated via reductions in energy intake, rather than depletion of energy stores. Evidence suggests that these mechanisms are not necessarily part of a homeostatic feedback system designed to regulate body weight or even anti-starvation mechanisms per se. Though they may have evolved to prevent starvation, they appear to be more accurately described as anti-weight loss mechanisms, engaged with caloric restriction irrespective of the adequacy of energy stores. It is hypothesized that these factors may combine to create a biological disposition that fosters the maintenance of an elevated body weight and work to restore the highest sustained body weight, thus precluding the long-term success of behavioral weight loss. It may be necessary to develop interventions that attenuate these biological mechanisms in order to achieve long-term weight reduction in obese individuals.
Forty-five million Americans attempt weight loss diets each year (1). Traditional cognitive-behavioral therapy-based “lifestyle change” diets often lead to weight loss and medically significant reductions in comorbidities (2). However, up to 50% of lost weight is typically regained by 1-year follow up, with nearly all remaining lost weight regained thereafter in the vast majority of individuals (3). This almost ubiquitous weight regain is witnessed in virtually every clinical weight loss trial, including those specifically aimed at improving weight loss maintenance (4, 5). Even the most well executed and empirically driven efforts to improve the sustainability of behavioral interventions have met with little success (5, 6). Without knowledge of the factors contributing to the long-term failure of behavioral approaches, investigators are limited in their ability to improve the sustainability of these interventions.
The focus of this manuscript is on biological pressures that may contribute to weight regain in obese or formerly obese individuals following behavioral weight loss. As behavioral weight loss remains the overwhelming treatment of choice for obese individuals (1), the discussion in this manuscript addresses the prototypical obese individual living in an industrialized nation who is able to achieve short-term success via energy restrictive diets, but is unable to maintain significant weight loss in the long-term. Factors contributing to initial weight gain, such as genetic predisposition and the food environment, are not discussed; however, it is important to note that the biological pressures to regain lost weight interact with these critical factors to determine the rate and amount of weight regain for each individual (7). Nonetheless, despite large inter-individual variability in genetic and environmental influences, the consistency of weight regain following behavioral weight loss in obese individuals suggests the influence of highly potent biological mechanisms that are consistent across nearly all individuals.
Conventional thought was that human biology included homeostatic feedback mechanisms designed to regulate body weight (8, 9). The average adult gains approximately 0.5 kg per year, which tranlates to approximately 3500 kcal surplus (10-13). Given average consumption of approximately 900,000 kcal per year (10, 11), this translates into only about 0.5% discrepancy, suggesting that homeostatic regulation of energy balance is relatively tight (14). However, the recent rapid spike in obesity rates calls into question the reliability of homeostatic regulation. With evidence that human biology evolved with a preference for energy intake and storage vs. expenditure (9, 15), it was recognized that these “regulatory” mechanims may reflect the same bias (9, 15, 16). As such, some investigators have proposed that these mechanisms may be more accurately described as “anti-starvation mechanisms” rather than regulatory mechanisms (17, 18). However, evidence in this manuscript suggests that the presence of adequate energy stores does not preclude the engagement of biological factors that contribute to weight regain. Thus, “anti-starvation mechanisms” may be as much of a misnomer as “regulatory mechanisms.”
Only recently have there been attempts to identify these individual biologial mechanisms and how they may contribute to weight regain. The mechanisms to be discussed include adipose cellularity, endocrine function, energy metabolism, neurobiology, and addiction-like mechanisms. It should be noted that causal connections between these factors and weight regain following behavioral weight loss remain largely untested. Thus, this manuscript was written as a theoretical article, presenting potential mechanisms for weight regain. The primary goal of this discussion is to promote further study of the potential causal role of these factors in weight regain and encourage the exploration of treatments that may circumvent or counter these biological mechanisms to prevent them from undermining healthy weight loss in obese individuals.
Excess weight gain typically leads to changes in body composition, including significant alterations in adipose cellularity. Although increases in body mass index (BMI) do not directly predict an absolute increase in body fat content (19), elevated body weight is generally associated with an increase in the diameter of fat cells (hypertrophy), as well as greater amounts of fat (triglycerides) stored within (20, 21). Most literature points to adipocyte hypertrophy as the main feature of obesity; however, alterations in adipocyte number may also be important (22, 23). Upon reaching an upward critical limit in fat cell volume, enlarged adipocytes (fat cells) secrete paracrine factors that induce preadipocyte proliferation (hyperplasia) (24-26). Thus, excess caloric intake may lead to increases in fat cell size and subsequent increases in fat cell number (20, 26, 27). Recent evidence suggests that hyperplasia may occur in overweight (but not obese) individuals (28). However, the preponderance of evidence suggests that hyperplasia occurs primarily in clinically severely obese individuals (27, 29, 30). Thus, if hyperplasia is associated with weight regain, this effect may be relegated to weight regain following weight loss in [formerly] clinically severely obese individuals, for whom returning to a lean body weight through behavioral weight loss is exceedingly difficult (31).
With behavioral weight loss, adipocyte hypertrophy decreases; however, the hyperplasia remains (20, 29, 32-35). Thus, weight loss dieting may reduce the size but not the number of fat cells. A lack of programmed cell death may be responsible for the failure of reductions in fat mass via nonsurgical means to reduce adipocyte number (20, 33). Therefore, relative to never obese individuals, weight-suppressed [formerly] obese individuals (particularly clinically severely obese individuals) may be left with a significantly greater number of adipocytes, which cannot be reduced via behavioral weight loss (34). See Table 1. Liposuction is the only known treatment able to reduce adipocyte number, but carries high complication rates (36).
It is not yet definitively known whether hyperplasia encourages weight regain in weight-suppressed individuals. There is some evidence to suggest that the presence of smaller adipocytes may encourage weight regain by decreasing the overall rate of fat oxidation and increasing the retention of ingested fuel (37-41). Normally, during times of energy deprivation, lipid (fat) stores break down triglycerides into their individuals components, glycerol and free fatty acids (42), which generate energy for the cell. However, the rate of lipolysis (fat breakdown) appears to be related to adipocyte size and cellular surface area (43); smaller cells exhibit lower rates of basal lipolysis (44). Therefore, if size-reduced adipocytes are modified to break down less and store more fat, these cells may expand and promote further proliferation. Although still speculative, there is some evidence to suggest that these cells may be predisposed to reach a particular mean size, allowing them to store similar amounts of lipid as previously formed adipocytes (25, 34). However, small adipocyte number may be sufficient to observe a clinically significant effect in only a percentage of obese (i.e., clinically severely obese) individuals.
An additional line of evidence reports higher levels of insulin in newly size-reduced adipocytes (44, 45). Insulin, which is excreted from pancreatic beta cells in response to rising levels of glucose in the bloodstream, facilitates a preferential utilization of carbohydrates to meet the cell’s energy requirements (40, 46-48). In addition, insulin inhibits lipolysis (49) and stores triglycerides in adipocytes (lipogenesis) (50). Interestingly, although insulin sensitivity seems to improve in weight-reduced individuals, fat metabolism slows, potentially in an attempt to preserve energy stores (37, 38, 49, 50). As a result of these changes in carbohydrate and fat utilization, an abnormal accumulation of triglycerides may give rise to a higher net fat cell content and elevations in body weight (37, 38, 51-53).
Adipocyte size is also correlated with plasma leptin concentrations, which have been shown to affect weight loss maintenance (54). Relative to control, formerly obese weight suppressed participants were found to have reduced fat cell volume and serum leptin levels, despite almost identical percent body fat (35). Because smaller adipocytes in formerly obese individuals may be secreting less leptin following behavioral weight loss (28, 35, 37, 55), an association between increased number of smaller adipocytes and leptin insufficiency has been proposed (28, 35, 37, 55, 56). Although leptin levels are not entirely depleted in weight suppressed formerly obese individuals, their secretions are much more attenuated relative to lean subjects who undergo caloric restriction (35, 55). Thus, with reductions in leptin secretion, heightened appetite and excess food intake may lead to weight regain (28, 54). The potential role of leptin in weight regain is further discussed below.
Leptin levels are reduced within 24 hours of energy restriction (57) and a number of studies report greater reductions of leptin than would be expected for given losses of adipose tissue (34, 35, 58). It has been suggested that leptin’s primary role is the prevention of starvation, rather than weight regulation per se, questioning the notion of “leptin resistance” (18). Reductions in leptin levels appear to trigger a starvation defense response, despite the persistance of abundant fat stores (57). Evidence suggests that there may be a threshold below which the “anti-starvation” action of leptin is enacted, and this threshold is proposed to increase concurrently with increases in adipose tissue (57). Thus, weight loss dieting in obese individuals may lead to leptin depletion (sub-threshold levels), despite the persistence of relatively high levels of leptin. Sub-threshold leptin levels result in reductions in metabolic rate and physical activity (14), as well as increases in hunger and food intake (59). Thus, behavioral weight loss and weight loss maintenance are accompanied by physiological attributes that resemble those of a leptin-deficient animal: lower energy expenditure, increased hunger, reduced thyroid metabolism, and diminished sympathetic nervous activity (60, 61).
Other Neuroendocrine Signals
In addition to insulin and leptin, a number of hormones secreted from the gastrointestinal tract and adipose tissue have been implicated in the modulation of appetite, food intake, energy expenditure, and body weight (62). Ghrelin, for example, induces hunger (63), while peptide YY3-36 (PYY) and cholecystokinin (CCK) promote satiety (64). Both increases in the orexigenic hormone ghrelin, and decreases in the postprandial satiety signals PYY and CCK, have been observed in weight-reduced individuals (65, 66). Thus, weight loss could induce a simultaneous decrease in satiety and increase in hunger, potentially encouraging formerly obese individuals to overeat and regain lost weight (58). See Table 1. Less consistently, weight loss in obese individuals has been shown to reduce thyroid hormone levels (67, 68), while hypothalamic-pituitary-adrenal (HPA) axis activity is increased (69, 70). Because thyroid hormone is implicated in increasing metabolic rate (71), decreased thyroid hormone levels may also contribute to simultaneous decreases in fat breakdown and increases in fat storage. As the HPA regulates stress-related elevations in cortisol, increases in this type of hormonal signaling can lead to increased appetite, fat accumulation and potentially, weight regain (72). Finally, catecholamine (epinephrine, norepinephrine) release, indicative of sympathetic activity, may also play a role. Weight-suppressed obese individuals show reductions in muscle sympathetic nerve activity responsible for the regulation of energy expenditure (67, 73, 74). With less circulating epinephrine and norepinephrine, lipid oxidation could be compromised due to decreased heart rate, blood flow, and oxygen delivery to muscle tissues. As suggested, this shift in metabolic activity (stunted triglyceride mobility) may encourage fat storage and weight regain.
Behavioral weight loss necessarily results in the loss of metabolic tissue (both fat and lean mass), resulting in reductions in energy expenditure (60, 75). Although not unequivocal (76, 77), the majority of studies report that behavioral weight loss results in significantly greater reductions in resting and total energy expenditure than would be expected for given losses in metabolic mass, suggesting “metabolic adaptation” (60, 78-82). Thus, energy expenditure during weight loss maintenance may be disproportionately reduced relative to body mass and composition, which may be largely attributable to increased skeletal muscle work efficiency (83). In fact, increases in metabolic efficiency have been reported within hours of caloric restriction, prior to any loss of metabolic tissue (84). In order to overcome this metabolic adaptation, obese individuals would need to continually reduce energy intake and maintain energy intake below that of never obese individuals at the same BMI.
An additional theory points to changes in body composition that may result from the cycles of weight loss and regain endemic to most obese individuals. There is some evidence that the fat-to-lean ratio of mass regained during weight regain is higher than that of the mass lost initially during weight loss diet (85). Thus, with each successive “weight cycle,” and individual’s overall body composition may begin to favor fat vs. lean mass (86). Given the higher contribution of lean vs. fat mass to energy expenditure, such increases in the fat to lean tissue ratio would lead to a decrease in metabolic rate and increase the amount of surplus energy stored (87). Weight cycling has been shown to increase lipogenic enzymes and decrease leptin in rodents (87), but a causal connection with weight regain has not been established. In humans, mostly limited cross-sectional or single-cycle data has been collected, all of which are inconclusive in regards to weight cycling and enhanced weight regain (86, 88). Some prospective studies report associations between weight cycling and lower metabolic rate (89) and weight regain (90); however, the evidence is mixed (87, 91). Thus, the potential contributions of changes in energy metabolism to weight regain remain speculative. See Table 1.
Food intake is primarily mediated by three interactive neural systems, the homeostatic, reward-related and inhibitory systems. The homeostatic system, comprised mainly of the hypothalamus, drives eating in response to caloric need in order to maintain energy balance. Alternatively, the reward-related system drives eating based on the perceived reward value of food, processed primarily through dopaminergic signaling in the mesolimbic pathway. The inhibitory system, comprised primarily of the dorsolateral prefrontal cortex, is associated with behavioral inhibition and processes attempts to inhibit excess food intake (i.e., dietary restraint) (92). Access to sufficient sustenance is commonplace in most industrialized nations, obviating the need for most homeostatic-driven eating (93). However, the homeostatic system serves to up-regulate the reward-system to increase the perceived reward value of food in response to energy restriction, encouraging the consumption of more high- vs. low- calorie foods and weight regain (94, 95). With energy surplus, there does appear to be an attempt to down-regulate reward-related signaling, which may combine with cognitive restraint represented by inhibitory signaling (95, 96). However, considerable evidence demonstrates that reward-related signaling easily overrides restrictive homeostatic and inhibitory signaling (97), driving food intake despite regulatory signals aimed at preventing excess caloric intake (93, 97). Thus, the hierarchical supremacy of the reward-related system illustrates the same biological bias towards the intake and storage of energy (15). Importantly, it appears as though the neural propensity to consume more high- vs. low- calorie foods persists after behavioral weight loss (54, 98), and may contribute to weight regain. Further, there is some evidence to suggest that neural changes associated with behavioral weight loss may actually increase the neural drive to consume high-calorie foods (54), as discussed below.
Dietary restraint and inhibitory neural responsivity are acutely increased through behavioral weight loss treatment (54, 96, 99). The typical short-term success of behavioral interventions suggests that this increase in inhibitory responsivity (dietary restraint) is temporarily able to overcome the neurobiological drives to consume palatable high-calorie foods. However, decreases in dietary restraint typically follow the cessation of behavioral weight loss treatment are directly associated with weight regain (100), implicating post-treatment erosion of inhibitory neural responsivity in weight regain. Recent evidence also indicates that reward-related neural signaling is activated in conjunction with inhibitory signaling (101, 102), suggesting that reward-related neural responsivity may be increased concurrently with inhibitory responsivity during behavioral weight loss treatment. Increased reward-related responsivity to food cues is seen within hours of caloric restriction (94) and nonsurgical weight loss has been shown to increase reward-related responsivity to food cues (54). See Table 1. This increase in reward-related neural responsivity likely reflects the common increased desire for “forbidden foods” in dieting individuals (103), and illustrates a potential mechanism for the eventual erosion of dietary restraint and subsequent weight regain following behavioral weight loss.
Addiction-Like Neural Mechanisms
Obesity is associated with increased preference for, and consumption of, foods high in fat and sugar (104). It has been speculated that these foods may have addictive properties, similar to those of drugs of abuse (105). Whether the clinical and diagnostic features of addiction can be applied to chronic food intake is a topic of heavy debate (106-108). Withdrawal symptoms commonly seen in addicted mice deprived of their drug of choice have been seen in mice allowed to binge on sugar solutions and then deprived of it, including teeth chattering and head shakes (105). Humans trying to cut back on high-fat and sugar containing foods report unpleasant physical and psychological sensations commonly reported by substance abusers deprived of their drug of choice, including restlessness, insatiable cravings, fatigue and poor mood (109). Self-identified refined food addicts report eating to alleviate feelings of agitation, depression, anxiety, headache, stress and fatigue, which some interpret as psychological manifestations of withdrawal (109). When shown pictures of palatable foods, food addicts identified by the Yale Food Addiction Scale (110) showed activation in the same areas (anterior cingulate gyrus and amygdala) as cocaine addicts shown pictures of crack cocaine, which is proposed to represent the neural correlates of cravings (111). Recent evidence from rodent studies indicates that obesity causes potentially permanent changes in brain reward circuitry that may underlie the cravings and anxiety associated with food withdrawal (106). It is important to note, however, that the symptoms associated with withdrawal from substances of abuse and palatable food are not indistinguishable. For instance, opiate withdrawal is often accompanied by muscle aches/cramping, increased tearing, insomnia, runny nose, yawning, diarrhea, nausea/vomiting, goose bumps and dilated pupils, none of which have been reported in humans undergoing caloric restriction (110, 112-114). Further, it is unclear how many obese individuals would qualify for a diagnosis of food addiction, if it exists.
Regardless of whether food addition per se exists, chronic overeating also resembles substance abuse in several additional ways, such as its continued occurrence despite medical and health consequences (115). Analogous to chronic alcohol abusers who stand at higher risks for liver and cardiovascular disease, obese individuals are at increased risk for a number of disorders, including hypertension, diabetes and cardiovascular disease (116). As with substance abusers who typically display frequent attempts to reduce usage, US adults attempt an average of seven weight loss diets in their lifetime (1). Furthermore, rates of weight regain in weight-reduced obese individuals are very reminiscent of the high relapse rates for drug addiction (117, 118), which may relate to the rewarding aspects of the substance (food or drug) and the potential for [neural] habituation to these rewarding aspects (2, 118), discussed below.
Importantly, studies consistently show progressive increases in the amount of substance consumed in chronic substance abusers (119). Similarly, portions sizes tend to increase with the development of obesity (120). Evidence suggests that this increase in usage may be due to habituation to the rewarding aspects of the food or drug (121, 122). Reward experienced from both substances of abuse and palatable foods is thought to result from striatal dopamine (DA) release from the ventral tegmental area to the nucleus accumbens within the dorsal striatum (123). Recent evidence suggests that that chronic stimulation of the dopamine D2 receptor results in reduced striatal DA terminal density (124, 125), and downregulation of the striatal D2 receptors (125). Evidence also suggests that both substance abusers and chronic overeaters increase usage (consumption) in order to make up for this habituation-induced deficit in reward (121, 122). Thus, chronic consumption of highly palatable foods may trigger addiction-like neuroadaptive responses in brain reward circuitries that drive compulsive and chronic overeating (121, 126).
Recent evidence suggests that reductions in experienced reward also persist in weight reduced formerly obese individuals (127), potentially contributing to weight regain. Interestingly, as alluded to in the previous section, users vs. non-users still show elevated reward responsivity to cues (i.e., wanting) associated with drugs and palatable food (122), potentially due to superconsolidation of the initial associations between the substance of abuse and resulting feelings of pleasure (122). Thus, chronic substance users and overeaters appear to be hyper-responsive to drug/food cues, but hypo-responsive to drug/food intake (128), both of which appear to persist after periods of non-use and may encourage recidivism. See Table 1. There is also evidence to suggest that chronic substance abusers display deficits in inhibitory signaling, which may contribute to the eventual failure of attempts to abstain (129); however, it remains unclear whether this is in-born or develops as a consequence of chronic overconsumption. Nonetheless, disinhibition, or the loss of control following consumption of a small amount of the pleasurable stimuli, is endemic to both substance abusers and chronic overeaters (130). Finally, recent evidence in rodents suggests that the permanent changes in reward-related neurocircuitry resulting from chronic overconsumption may be related to overconsumption-related increases in the permeability of the blood brain barrier, allowing potentially damaging elements to enter the brain (131). However, this hypothesis remains speculative until further studies can be conducted.
Changes in adipose cellularity and addiciton-like neural habituation result from chronic overconsumption and appear irreversable via behavioral weight loss (24, 34, 122, 129). Thus, these factors are not activated to prevent weight loss but serve to encourage preservation of highest sustained body weight, and may actually promote indefinite increases in energy storage. Alterations in endocrine function (e.g., decreases in leptin and increases in ghrelin), decreases in energy expenditure, and increases in neural responsivity to high-calorie food cues all occur within 24 hours of caloric restriction (Table 1) (57, 84, 132). Regardless of when these mechansism are activated, each has the potential to exert a [neuro]biological influence that may reduce an obese or formerly obese individual’s ability to maintain behavioral weight losses and promote weight regain at least to the individual’s highest sustained lifetime weight. These influences also carry the expected weight regain promoting behavioral correlates. Weight-reduced vs. never-obese subjects report increased food craving (133), a decreased perception of amount eaten (134), decreased postprandial satiety (135) and an increased preference for calorically dense foods (136). With these additional biological influences encouraging the consumption and storage of energy, it is not surprising that weight regain following behavioral weight loss occurs at a faster rate than initial weight gain (135, 137).
These mechanisms appear not to be part of a highly sensitive homeostatic feedback system designed to regulate body weight at any particular “set point,” but mechanisms either aquired via excess weight gain or enacted almost immediately via reduced caloric intake. Importantly, these mechansims operate irrespective of the adequacy of energy stores. Thus, these mechanisms may be more accurately described as anti-weight loss mechanisms, rather than anti-starvation mechansims per se. Regardless, these systems are engaged with very rare exception, and appear not to descriminate by sex, BMI or even genetic makeup. Thus, the consistency of the influence of these mechanisms appears to mirror the consistency of weight regain in weight reduced [formerly] obese individuals (138). Discussion of these factors illustrates the importance of obesity prevention efforts. This is particularly true for children and adolescents, where rates of obesity have seen disproportionately high increases in recent years (139).
Ultimately, the biological forces to maintain highest body weight, resist weight loss and regain lost weight appear insurmountable for most individuals attempting to lose weight through behavioral interventions (138). The presence of these biological forces may explain why relatively drastic surgical procedures (e.g., Roux-en-Y gastric bypass) are the only form of intervention for obesity demonstrating long-term efficacy. Further, it may not be a coincidence that significant changes in several of these mechanisms (e.g., endocrine function (140) and neural responsivity (141)) have been reported following obesity surgery (142). Thus, it may be necessary to circumvent at least some of these biological mechanisms in order to achieve sustainable weight loss.
It is important to note that the hypothesis presented in this paper does not propose to account for individual differences in weight gain over the lifespan. Nor does it attempt to explain the rapid increase in obesity rates in the past 30 years. These issues have been discussed at length in other published work, which are typically explained by differences in genetic makeup and changes in the food environment, respectively (143, 144). The focus of this paper was intentionally relegated to the biological mechanisms consistent across all individuals that may contribute to weight regain. Thus, the concepts discussed here do not explain obesity or individual differences in weight gain, but attempt to offer some potential explanation for the astounding consistency of weight regain following weight loss in obese or formerly obese individuals. We believe that the evidence suggests that the biological pressures discussed here would be more accurately described as pressures to sustain sufficient caloric intake to maintain homeostasis (weight stability) at an individual’s highest sustained body weight, rather than to regain lost weight per se.
Most obese individuals are able to utilize current behavioral techniques, which have been honed through decades of research and experimentation to maximize their effectiveness, to overcome these biological pressures for a relatively short time (typically a few months) and lose some (typically 5-10% initial) weight (2, 4, 145). Eventually, however, these biological pressures win out, as so called “diet fatigue” sets in and individuals are no longer able to maintain the level of cognitive and behavioral discipline necessary to overcome unyielding (and potentially mounting) biological pressures to return to their highest sustained body weight. However, we feel it vital to stress the importance of the necessary interaction between these biological pressures, genetic makeup and the food environment. Although nearly all obese and formerly obese individuals regain weight following behavioral weight loss, some do not (99, 146). Further, those that do regain lost weight, do so at different rates (5). This may be explained by a myriad of different psychological and social factors but is most likely explained by individual differences in genetic makeup and the food environment.
Part of the purpose of this review was to incite further thought and research, as several questions naturally stem from the evidence and theories presented. For example, how might the food environment moderate the effects of these responses, how long do these regulatory responses persist, and can these mechanisms be “reset” so the body defends a healthy (or even just overweight) vs. obese body weight? We would suggest that a toxic or “obesogenic” food environment, such as that currently seen in the US, is neither necessary nor sufficient for weight regain but is a very potent contributing (moderating) factor that makes weight regain much more likely. Few would argue against the notion that a toxic food environment contributes to weight gain, regardless of whether it was preceded by weight loss. However, further research may determine whether this effect is more or less strong for weight suppressed vs. never obese individuals. The evidence presented in this review seems to suggest that these biological pressures toward weight regain persist until caloric intake returns to the level it was at when the individual was at their highest maintained body weight. There is some speculation that gastric bypass (and possibly sleeve gastrectomy) surgery may “reset” some of these mechanisms so that they either do not operate to drive weight regain or at least not operate to the same extent to which they would following behavioral weight loss (147). For example, gastric bypass surgery has been shown to dramatically alter gut peptide signaling (140, 142, 148) and neural responsivity (141, 149, 150), both of which have been shown to be associated with decreased desire to eat calorically-dense foods following surgery (150, 151). Other recent evidence suggests that bypass surgery vs. behavioral weight loss results in greater decrease in circulating amino acids, which may contribute to improvements in glucose homeostasis and sustained weight loss (152). We will look to current and future research to lend support for or refute these hypotheses.
The weight regain promoting actions of the mechanisms discussed in this manuscript remain largely speculative, as evidence demonstrating causal relations between these factors and weight regain is lacking. Future research should seek to elucidate and quantify the contribution of each of these factors, with the goal of developing ways to circumvent those with the greatest contribtion to weight regain. One possibililty may be to identify how bariatric surgery alters some these mechanisms and attempt to replicate this action through nonsurgical means (141, 153). Other factors are likely involved and require more study, particularly the potential moderating effects of the food environment. Additional important factors may include the potential for increased drive to eat, decreased drive to be physically active, altered sympathetic/parasymphathetic tone, and altered gut microflora (154). Future work should also address the possibility that these mechansims act syngeristically to create a biological profile for which weight regain in weight reduced obese individuals is almost inevitable. Finally, future research may also look to determine how long an elevated body weight must be maintained before these biological mechanisms begin to defend that weight.
We have presented evidence that the likelihood of weight regain in weight suppressed obese and formerly obese individuals may be increased by a confluence of biological mechanisms, including increased metabolic efficiency, changes in neuroendocrine signaling (e.g., decreased satiety signaling), and changes in neural responsivity to both food cues (e.g., increased reward-related or decreased inhibitory anticipatory responsivity) and food intake (e.g., decreased consummatory reward through habituation to the rewarding aspects of palatable food). These biological pressures that may undermine weight loss efforts and promote weight regain are almost immediately enacted in obese individuals attempting even modest and healthy weight reduction. Further, these mechanisms operate invariably and appear to defend an individual’s highest sustained body weight. Thus, it is the opinion of these authors that these mechanisms would be more accurated describe as anti-weight loss mechanisms rather than anti-starvation mechanisms. Regardless, obese individuals face an extreme uphill battle in having to overcome powerful biological drives that appear insurmountable via behavioral interventions, illustrating the critical importance of obesity prevention efforts for normal and overweight individuals. This may be particularly pertinent to parents of overweight children, who are significantly more likely to become obese adults (155). It is our hope that future research will further elucidate these mechanisms and provide the opportunity for the development of interventions that counter these mechanisms and enable long-term behavioral weight loss maintenance.
Dr. Ochner is supported by NIH grant KL2RR024157. Dr. Pi-Sunyer and the New York Obesity Nutrition Research Center are supported by NIH grant P30DK26687. The authors would also like to thank Dr. Michael Rosenbaum for providing and suggesting a number of resources for this manuscript.
Disclosure: The authors have no potential conflicts of interest.
1. Inc. G [cited 2011 May 12];Six in ten Americans have dieted to lose weight. 2005 Gallup Poll]. Available from: http://www.gallup.com/poll/17890/six-americans-attempted-lose-weight.aspx.
2. Foster GD, Makris AP, Bailer BA. Behavioral treatment of obesity. Am J Clin Nutr. 2005 Jul;82:230S–5S. [PubMed]
3. Wadden T, Sarwer D. Behavioral treatment of obesity: new approaches to an old disorder. In: Goldstein D, editor. The Management of Eating Disorders. Humana Press; Totowa, NJ: 1996.
4. Wilson G, Brownell KD. Behavioral treatment for obesity. In: Fairburn CB, Brownell KD, editors. Eating Disorders and Obesity: A Comprehensive Handbook. The Guilford Press; New York: 2002. pp. 524–8.
5. Sarlio-Lähteenkorva S, Rissanen A, Kaprio J. A descriptive study of weight loss maintenance: 6 and 15 year follow-up of initially overweight adults. Int J Obes Relat Metab Disord. 2000 Jan;24:116–25. [PubMed]
6. Lowe M. The effect of training in reduced energy density eating and food self-monitoring accuracy on weight loss maintenance. Obesity (Silver Spring, Md) 2008;16:2016–23. [PubMed]
7. Votruba SB, Blanc S, Schoeller DA. Pattern and cost of weight gain in previously obese women. Am J Physiol Endocrinol Metab. 2002 Apr;282:E923–30. [PubMed]
8. Speakman JR, Levitsky DA, Allison DB, Bray MS, de Castro JM, Clegg DJ, Clapham JC, Dulloo AG, Gruer L, et al. Set points, settling points and some alternative models: theoretical options to understand how genes and environments combine to regulate body adiposity. Dis Model Mech. 2011 Nov;4:733–45. [PMC free article] [PubMed]
9. Hall KD, Heymsfield SB, Kemnitz JW, Klein S, Schoeller DA, Speakman JR. Energy balance and its components: implications for body weight regulation. Am J Clin Nutr. 2012 Apr;95:989–94. [PMC free article] [PubMed]
10. Du H, van der A DL, Ginder V, Jebb SA, Forouhi NG, Wareham NJ, Halkjaer J, Tjønneland A, Overvad K, et al. Dietary energy density in relation to subsequent changes of weight and waist circumference in European men and women. PLoS One. 2009;4:e5339. [PMC free article] [PubMed]
11. Forouhi NG, Sharp SJ, Du H, van der A DL, Halkjaer J, Schulze MB, Tjønneland A, Overvad K, Jakobsen MU, et al. Dietary fat intake and subsequent weight change in adults: results from the European Prospective Investigation into Cancer and Nutrition cohorts. Am J Clin Nutr. 2009 Dec;90:1632–41. [PubMed]
12. Lewis CE, Jacobs DR, McCreath H, Kiefe CI, Schreiner PJ, Smith DE, Williams OD. Weight gain continues in the 1990s: 10-year trends in weight and overweight from the CARDIA study. Coronary Artery Risk Development in Young Adults. Am J Epidemiol. 2000 Jun;151:1172–81. [PubMed]
13. Pietrobelli A, Allison DB, Heshka S, Heo M, Wang ZM, Bertkau A, Laferrére B, Rosenbaum M, Aloia JF, et al. Sexual dimorphism in the energy content of weight change. Int J Obes Relat Metab Disord. 2002 Oct;26:1339–48. [PubMed]
14. Rosenbaum M, Kissileff HR, Mayer LE, Hirsch J, Leibel RL. Energy intake in weight-reduced humans. Brain Res. 2010 Sep;1350:95–102. [PMC free article] [PubMed]
15. Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Am J Hum Genet. 1962 Dec;14:353–62. [PMC free article] [PubMed]
16. Schwartz MW, Woods SC, Seeley RJ, Barsh GS, Baskin DG, Leibel RL. Is the energy homeostasis system inherently biased toward weight gain? Diabetes. 2003 Feb;52:232–8. [PubMed]
17. Prentice AM, Hennig BJ, Fulford AJ. Evolutionary origins of the obesity epidemic: natural selection of thrifty genes or genetic drift following predation release? Int J Obes (Lond) 2008 Nov;32:1607–10. [PubMed]
18. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS. Role of leptin in the neuroendocrine response to fasting. Nature. 1996 Jul;382:250–2. [PubMed]
19. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults--The Evidence Report National Institutes of Health. Obes Res. 1998 Sep;6(Suppl 2):51S–209S. [PubMed]
20. Martinsson A. Hypertrophy and hyperplasia of human adipose tissue in obesity. Pol Arch Med Wewn. 1969;42:481–6. [PubMed]
21. Hirsch J, Goldrick RB. Serial studies on the metabolism of human adipose tissue. I. Lipogensis and free fatty acid update and resease in small aspirated samples of subcutaneous fat. J Clin Invest. 1964 Sep;43:1776–92. [PMC free article] [PubMed]
22. Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Näslund E, et al. Dynamics of fat cell turnover in humans. Nature. 2008 Jun;453:783–7. [PubMed]
23. Sun K, Kusminski CM, Scherer PE. Adipose tissue remodeling and obesity. J Clin Invest. 2011 Jun;121:2094–101. [PMC free article] [PubMed]
24. Marques BG, Hausman DB, Martin RJ. Association of fat cell size and paracrine growth factors in development of hyperplastic obesity. Am J Physiol. 1998 Dec;275:R1898–908. [PubMed]
25. Faust IM, Johnson PR, Stern JS, Hirsch J. Diet-induced adipocyte number increase in adult rats: a new model of obesity. Am J Physiol. 1978 Sep;235:E279–86. [PubMed]
26. Tchoukalova YD, Votruba SB, Tchkonia T, Giorgadze N, Kirkland JL, Jensen MD. Regional differences in cellular mechanisms of adipose tissue gain with overfeeding. Proc Natl Acad Sci U S A. 2010 Oct 19;107:18226–31. [PMC free article] [PubMed]
27. Hirsch J, Batchelor B. Adipose tissue cellularity in human obesity. Clin Endocrinol Metab. 1976 Jul;5:299–311. [PubMed]
28. Singh P, Somers VK, Romero-Corral A, Sert-Kuniyoshi FH, Pusalavidyasagar S, Davison DE, Jensen MD. Effects of weight gain and weight loss on regional fat distribution. Am J Clin Nutr. 2012 Aug;96:229–33. [PMC free article] [PubMed]
29. Björntorp P, Carlgren G, Isaksson B, Krotkiewski M, Larsson B, Sjöström L. Effect of an energy-reduced dietary regimen in relation to adipose tissue cellularity in obese women. Am J Clin Nutr. 1975 May;28:445–52. [PubMed]
30. Ginsberg-Fellner F, Knittle JL. Weight reduction in young obese children. I. Effects on adipose tissue cellularity and metabolism. Pediatr Res. 1981 Oct;15:1381–9. [PubMed]
31. Monkhouse SJ, Morgan JD, Bates SE, Norton SA. An overview of the management of morbid obesity. Postgrad Med J. 2009 Dec;85:678–81. [PubMed]
32. Hirsch J, Han PW. Cellularity of rat adipose tissue: effects of growth, starvation, and obesity. J Lipid Res. 1969 Jan;10:77–82. [PubMed]
33. Gurr MI, Jung RT, Robinson MP, James WP. Adipose tissue cellularity in man: the relationship between fat cell size and number, the mass and distribution of body fat and the history of weight gain and loss. Int J Obes. 1982;6:419–36. [PubMed]
34. Arner P, Spalding KL. Fat cell turnover in humans. Biochem Biophys Res Commun. 2010 May;396:101–4. [PubMed]
35. Löfgren P, Andersson I, Adolfsson B, Leijonhufvud BM, Hertel K, Hoffstedt J, Arner P. Long-term prospective and controlled studies demonstrate adipose tissue hypercellularity and relative leptin deficiency in the postobese state. J Clin Endocrinol Metab. 2005 Nov;90:6207–13. [PubMed]
36. Castellano JJ, Jackson RF. A review of the complications of liposuction. American Journal of Cosmetic Surgery. 2011;28:204–2011.
37. MacLean PS, Higgins JA, Jackman MR, Johnson GC, Fleming-Elder BK, Wyatt HR, Melanson EL, Hill JO. Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient regain in obesity-prone rats. Am J Physiol Regul Integr Comp Physiol. 2006 Jun;290:R1577–88. [PubMed]
38. Jackman MR, Steig A, Higgins JA, Johnson GC, Fleming-Elder BK, Bessesen DH, MacLean PS. Weight regain after sustained weight reduction is accompanied by suppressed oxidation of dietary fat and adipocyte hyperplasia. Am J Physiol Regul Integr Comp Physiol. 2008 Apr;294:R1117–29. [PubMed]
39. Knittle JL, Hirsch J. Effect of early nutrition on the development of rat epididymal fat pads: cellularity and metabolism. J Clin Invest. 1968 Sep;47:2091–8. [PMC free article] [PubMed]
40. Kelley DE, Goodpaster B, Wing RR, Simoneau JA. Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol. 1999 Dec;277:E1130–41. [PubMed]
41. Berggren JR, Boyle KE, Chapman WH, Houmard JA. Skeletal muscle lipid oxidation and obesity: influence of weight loss and exercise. Am J Physiol Endocrinol Metab. 2008 Apr;294:E726–32. [PubMed]
42. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS. Regulation of lipolysis in adipocytes. Annu Rev Nutr. 2007;27:79–101. [PMC free article] [PubMed]
43. Arner P. Control of lipolysis and its relevance to development of obesity in man. Diabetes Metab Rev. 1988 Aug;4:507–15. [PubMed]
44. Smith U. Insulin responsiveness and lipid synthesis in human fat cells of different sizes: effect of the incubation medium. Biochim Biophys Acta. 1970 Dec;218:417–23. [PubMed]
45. Salans LB, Dougherty JW. The effect of insulin upon glucose metabolism by adipose cells of different size. Influence of cell lipid and protein content, age, and nutritional state. J Clin Invest. 1971 Jul;50:1399–410. [PMC free article] [PubMed]
46. Kelley DE, Goodpaster BH, Storlien L. Muscle triglyceride and insulin resistance. Annu Rev Nutr. 2002;22:325–46. [PubMed]
47. Tremblay A, Boulé N, Doucet E, Woods SC. Is the insulin resistance syndrome the price to be paid to achieve body weight stability? Int J Obes (Lond) 2005 Oct;29:1295–8. [PubMed]
48. Yost TJ, Jensen DR, Eckel RH. Weight regain following sustained weight reduction is predicted by relative insulin sensitivity. Obes Res. 1995 Nov;3:583–7. [PubMed]
49. Lazzer S, Vermorel M, Montaurier C, Meyer M, Boirie Y. Changes in adipocyte hormones and lipid oxidation associated with weight loss and regain in severely obese adolescents. Int J Obes (Lond) 2005 Oct;29:1184–91. [PubMed]
50. Nishino N, Tamori Y, Kasuga M. Insulin efficiently stores triglycerides in adipocytes by inhibiting lipolysis and repressing PGC-1alpha induction. Kobe J Med Sci. 2007;53:99–106. [PubMed]
51. Ballor DL, Harvey-Berino JR, Ades PA, Cryan J, Calles-Escandon J. Decrease in fat oxidation following a meal in weight-reduced individuals: a possible mechanism for weight recidivism. Metabolism. 1996 Feb;45:174–8. [PubMed]
52. Bessesen DH, Rupp CL, Eckel RH. Dietary fat is shunted away from oxidation, toward storage in obese Zucker rats. Obes Res. 1995 Mar;3:179–89. [PubMed]
53. Raben A, Andersen HB, Christensen NJ, Madsen J, Holst JJ, Astrup A. Evidence for an abnormal postprandial response to a high-fat meal in women predisposed to obesity. Am J Physiol. 1994 Oct;267:E549–59. [PubMed]
54. Rosenbaum M, Sy M, Pavlovich K, Leibel R, Hirsch J. Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli. The Journal of clinical investigation. 2008;118:2583–91. [PMC free article] [PubMed]
55. Shi H, Akunuru S, Bierman JC, Hodge KM, Mitchell MC, Foster MT, Seeley RJ, Reizes O. Diet-induced obese mice are leptin insufficient after weight reduction. Obesity (Silver Spring) 2009 Sep;17:1702–9. [PubMed]
56. Van Harmelen V, Reynisdottir S, Eriksson P, Thorne A, Hoffstedt J, Lonnqvist F, Arner P. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes. 1998 Jun;47:913–7. [PubMed]
57. Leibel RL. The role of leptin in the control of body weight. Nutr Rev. 2002 Oct;60:S15–9. discussion S68-84, 5-7. [PubMed]
58. Rosenbaum M, Nicolson M, Hirsch J, Murphy E, Chu F, Leibel RL. Effects of weight change on plasma leptin concentrations and energy expenditure. J Clin Endocrinol Metab. 1997 Nov;82:3647–54. [PubMed]
59. Kissileff HR, Thornton JC, Torres MI, Pavlovich K, Mayer LS, Kalari V, Leibel RL, Rosenbaum M. Leptin reverses declines in satiation in weight-reduced obese humans. Am J Clin Nutr. 2012 Feb;95:309–17. [PMC free article] [PubMed]
60. Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar;332:621–8. [PubMed]
61. Jéquier E. Leptin signaling, adiposity, and energy balance. Ann N Y Acad Sci. 2002 Jun;967:379–88. [PubMed]
62. Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG. Central nervous system control of food intake. Nature. 2000 Apr;404:661–71. [PubMed]
63. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG, Dhillo WS, Ghatei MA, Bloom SR. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab. 2001 Dec;86:5992. [PubMed]
64. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature. 2002 Aug;418:650–4. [PubMed]
65. Sumithran P, Prendergast LA, Delbridge E, Purcell K, Shulkes A, Kriketos A, Proietto J. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011 Oct;365:1597–604. [PubMed]
66. Lien LF, Haqq AM, Arlotto M, Slentz CA, Muehlbauer MJ, McMahon RL, Rochon J, Gallup D, Bain JR, et al. The STEDMAN project: biophysical, biochemical and metabolic effects of a behavioral weight loss intervention during weight loss, maintenance, and regain. OMICS. 2009 Feb;13:21–35. [PMC free article] [PubMed]
67. Rosenbaum M, Hirsch J, Murphy E, Leibel RL. Effects of changes in body weight on carbohydrate metabolism, catecholamine excretion, and thyroid function. Am J Clin Nutr. 2000 Jun;71:1421–32. [PubMed]
68. Kozłowska L, Rosołowska-Huszcz D. Leptin, thyrotropin, and thyroid hormones in obese/overweight women before and after two levels of energy deficit. Endocrine. 2004 Jul;24:147–53. [PubMed]
69. McKibbin PE, Cotton SJ, McMillan S, Holloway B, Mayers R, McCarthy HD, Williams G. Altered neuropeptide Y concentrations in specific hypothalamic regions of obese (fa/fa) Zucker rats. Possible relationship to obesity and neuroendocrine disturbances. Diabetes. 1991 Nov;40:1423–9. [PubMed]
70. Tomiyama AJ, Mann T, Vinas D, Hunger JM, Dejager J, Taylor SE. Low calorie dieting increases cortisol. Psychosom Med. 2010 May;72:357–64. [PMC free article] [PubMed]
71. Moreno M, de Lange P, Lombardi A, Silvestri E, Lanni A, Goglia F. Metabolic effects of thyroid hormone derivatives. Thyroid. 2008 Feb;18:239–53. [PubMed]
72. Björntorp P. Do stress reactions cause abdominal obesity and comorbidities? Obes Rev. 2001 May;2:73–86. [PubMed]
73. Straznicky NE, Grima MT, Eikelis N, Nestel PJ, Dawood T, Schlaich MP, Chopra R, Masuo K, Esler MD, et al. The effects of weight loss versus weight loss maintenance on sympathetic nervous system activity and metabolic syndrome components. J Clin Endocrinol Metab. 2011 Mar;96:E503–8. [PubMed]
74. Peterson HR, Rothschild M, Weinberg CR, Fell RD, McLeish KR, Pfeifer MA. Body fat and the activity of the autonomic nervous system. N Engl J Med. 1988 Apr;318:1077–83. [PubMed]
75. Gallagher D, Visser M, Wang Z, Harris T, Pierson RN, Heymsfield SB. Metabolically active component of fat-free body mass: influences of age, adiposity, and gender. Metabolism. 1996 Aug;45:992–7. [PubMed]
76. de Groot LC, van Es AJ, van Raaij JM, Vogt JE, Hautvast JG. Energy metabolism of overweight women 1 mo and 1 y after an 8-wk slimming period. Am J Clin Nutr. 1990 Apr;51:578–83. [PubMed]
77. Wyatt HR, Grunwald GK, Seagle HM, Klem ML, McGuire MT, Wing RR, Hill JO. Resting energy expenditure in reduced-obese subjects in the National Weight Control Registry. Am J Clin Nutr. 1999 Jun;69:1189–93. [PubMed]
78. Astrup A, Gøtzsche PC, van de Werken K, Ranneries C, Toubro S, Raben A, Buemann B. Meta-analysis of resting metabolic rate in formerly obese subjects. Am J Clin Nutr. 1999 Jun;69:1117–22. [PubMed]
79. Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes (Lond) 2010 Oct;34(Suppl 1):S47–55. [PMC free article] [PubMed]
80. Johannsen DL, Knuth ND, Huizenga R, Rood JC, Ravussin E, Hall KD. Metabolic slowing with massive weight loss despite preservation of fat-free mass. J Clin Endocrinol Metab. 2012 Jul;97:2489–96. [PMC free article] [PubMed]
81. Camps SG, Verhoef SP, Westerterp KR. Weight loss, weight maintenance, and adaptive thermogenesis. Am J Clin Nutr. 2013 Mar; [PubMed]
82. Tremblay A, Chaput JP. Adaptive reduction in thermogenesis and resistance to lose fat in obese men. Br J Nutr. 2009 Aug;102:488–92. [PubMed]
83. Rosenbaum M, Goldsmith R, Bloomfield D, Magnano A, Weimer L, Heymsfield S, Gallagher D, Mayer L, Murphy E, Leibel RL. Low-dose leptin reverses skeletal muscle, autonomic, and neuroendocrine adaptations to maintenance of reduced weight. J Clin Invest. 2005 Dec;115:3579–86. [PMC free article] [PubMed]
84. de Boer JO, van Es AJ, Roovers LC, van Raaij JM, Hautvast JG. Adaptation of energy metabolism of overweight women to low-energy intake, studied with whole-body calorimeters. Am J Clin Nutr. 1986 Nov;44:585–95. [PubMed]
85. Lee JS, Visser M, Tylavsky FA, Kritchevsky SB, Schwartz AV, Sahyoun N, Harris TB, Newman AB, Study HA. Weight loss and regain and effects on body composition: the Health, Aging, and Body Composition Study. J Gerontol A Biol Sci Med Sci. 2010 Jan;65:78–83. [PMC free article] [PubMed]
86. Lahti-Koski M, Männistö S, Pietinen P, Vartiainen E. Prevalence of weight cycling and its relation to health indicators in Finland. Obes Res. 2005 Feb;13:333–41. [PubMed]
87. Prentice AM, Jebb SA, Goldberg GR, Coward WA, Murgatroyd PR, Poppitt SD, Cole TJ. Effects of weight cycling on body composition. Am J Clin Nutr. 1992 Jul;56:209S–16S. [PubMed]
88. van der Kooy K, Leenen R, Seidell JC, Deurenberg P, Hautvast JG. Effect of a weight cycle on visceral fat accumulation. Am J Clin Nutr. 1993 Dec;58:853–7. [PubMed]
89. Manore MM, Berry TE, Skinner JS, Carroll SS. Energy expenditure at rest and during exercise in nonobese female cyclical dieters and in nondieting control subjects. Am J Clin Nutr. 1991 Jul;54:41–6. [PubMed]
90. Field AE, Manson JE, Taylor CB, Willett WC, Colditz GA. Association of weight change, weight control practices, and weight cycling among women in the Nurses’ Health Study II. Int J Obes Relat Metab Disord. 2004 Sep;28:1134–42. [PubMed]
91. Schmidt WD, Corrigan D, Melby CL. Two seasons of weight cycling does not lower resting metabolic rate in college wrestlers. Med Sci Sports Exerc. 1993 May;25:613–9. [PubMed]
92. Le DS, Pannacciulli N, Chen K, Del Parigi A, Salbe A, Reiman E, Krakoff J. Less activation of the left dorsolateral prefrontal cortex in response to a meal: a feature of obesity. The American journal of clinical nutrition. 2006;84:725–31. [PubMed]
93. Lowe M, Levine A. Eating motives and the controversy over dieting: eating less than needed versus less than wanted. Obesity (Silver Spring, Md) 2005;13:797–806. [PubMed]
94. LaBar KS, Gitelman D, Parrish T, Kim Y, Nobre A, Mesulam M. Hunger selectively modulates corticolimbic activation to food stimuli in humans. Behavioral neuroscience. 2001;115:493–500. [PubMed]
95. Berthoud HR. Metabolic and hedonic drives in the neural control of appetite: who is the boss? Curr Opin Neurobiol. 2011 Dec;21:888–96. [PMC free article] [PubMed]
96. Del Parigi A, Chen K, Salbe A, Hill J, Wing R, Reiman E, Tataranni P. Successful dieters have increased neural activity in cortical areas involved in the control of behavior. International journal of obesity (2005) 2007;31:440–8. [PubMed]
97. Petrovich G, Setlow B, Holland P, Gallagher M. Amygdalo-hypothalamic circuit allows learned cues to override satiety and promote eating. The Journal of neuroscience. 2002;22:8748–53. [PubMed]
98. Murdaugh DL, Cox JE, Cook EW, Weller RE. fMRI reactivity to high-calorie food pictures predicts short- and long-term outcome in a weight-loss program. Neuroimage. 2012 Feb;59:2709–21. [PMC free article] [PubMed]
99. Wing RR, Papandonatos G, Fava JL, Gorin AA, Phelan S, McCaffery J, Tate DF. Maintaining large weight losses: the role of behavioral and psychological factors. J Consult Clin Psychol. 2008 Dec;76:1015–21. [PMC free article] [PubMed]
100. McGuire M, Wing R, Klem M, Lang W, Hill J. What predicts weight regain in a group of successful weight losers? J Consult Clin Psychol. 1999;67:177–85. [PubMed]
101. Stice E, Spoor S, Bohon C, Veldhuizen MG, Small DM. Relation of reward from food intake and anticipated food intake to obesity: a functional magnetic resonance imaging study. J Abnorm Psychol. 2008 Nov;117:924–35. [PMC free article] [PubMed]
102. Burger K, Stice E. Relation of dietary restraint scores to activation of reward-related brain regions in response to food intake, anticipated intake, and food pictures. NeuroImage (Orlando, Fla) 2011;55:233–9. [PMC free article] [PubMed]
103. Soetens B, Braet C, Van Vlierberghe L, Roets A. Resisting temptation: effects of exposure to a forbidden food on eating behaviour. Appetite. 2008 Jul;51:202–5. [PubMed]
104. Drewnowski A. Intense sweeteners and energy density of foods: implications for weight control. Eur J Clin Nutr. 1999 Oct;53:757–63. [PubMed]
105. Avena NM, Rada P, Hoebel BG. Sugar and fat bingeing have notable differences in addictive-like behavior. J Nutr. 2009 Mar;139:623–8. [PMC free article] [PubMed]
106. Sharma S, Fernandes MF, Fulton S. Adaptations in brain reward circuitry underlie palatable food cravings and anxiety induced by high-fat diet withdrawal. Int J Obes (Lond) 2012 Dec; [PubMed]
107. Corsica JA, Pelchat ML. Food addiction: true or false? Curr Opin Gastroenterol. 2010 Mar;26:165–9. [PubMed]
108. Gold MS, Graham NA, Cocores JA, Nixon SJ. Food addiction? J Addict Med. 2009 Mar;3:42–5. [PubMed]
109. Ifland JR, Preuss HG, Marcus MT, Rourke KM, Taylor WC, Burau K, Jacobs WS, Kadish W, Manso G. Refined food addiction: a classic substance use disorder. Med Hypotheses. 2009 May;72:518–26. [PubMed]
110. Gearhardt AN, Corbin WR, Brownell KD. Preliminary validation of the Yale Food Addiction Scale. Appetite. 2009 Apr;52:430–6. [PubMed]
111. Gearhardt AN, Yokum S, Orr PT, Stice E, Corbin WR, Brownell KD. Neural correlates of food addiction. Arch Gen Psychiatry. 2011 Aug;68:808–16. [PMC free article] [PubMed]
112. Tintinalli J, Stapczynski J, Ma OJ, Cline D, Cydulka R, Meckler G. In: Emergency Medicine: A Comprehensive Study Guide. 6th ed Tintinalli J, editor. McGraw-Hill; New York, NY: 2004.
113. DG G, BO G, VL S. Withdrawal symptoms: individual differences and similarities across addictive behaviors. Personality and Individual Differences. 1998;24:351–6.
114. Gossop M, Griffiths P, Bradley B, Strang J. Opiate withdrawal symptoms in response to 10-day and 21-day methadone withdrawal programmes. Br J Psychiatry. 1989 Mar;154:360–3. [PubMed]
115. Lawrence VJ, Kopelman PG. Medical consequences of obesity. Clin Dermatol. 2004 Jul-Aug;22:296–302. 2004. [PubMed]
116. Bray GA. Medical consequences of obesity. J Clin Endocrinol Metab. 2004 Jun;89:2583–9. [PubMed]
117. McLellan AT, Lewis DC, O’Brien CP, Kleber HD. Drug dependence, a chronic medical illness: implications for treatment, insurance, and outcomes evaluation. JAMA. 2000 Oct;284:1689–95. [PubMed]
118. Anderson JW, Konz EC, Frederich RC, Wood CL. Long-term weight-loss maintenance: a meta-analysis of US studies. Am J Clin Nutr. 2001 Nov;74:579–84. [PubMed]
119. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010 Jan;35:217–38. [PMC free article] [PubMed]
120. Young LR, Nestle M. The contribution of expanding portion sizes to the US obesity epidemic. Am J Public Health. 2002 Feb;92:246–9. [PubMed]
121. Volkow ND, Wang GJ, Fowler JS, Telang F. Overlapping neuronal circuits in addiction and obesity: evidence of systems pathology. Philos Trans R Soc Lond B Biol Sci. 2008 Oct;363:3191–200. [PMC free article] [PubMed]
122. Wang GJ, Volkow ND, Thanos PK, Fowler JS. Similarity between obesity and drug addiction as assessed by neurofunctional imaging: a concept review. J Addict Dis. 2004;23:39–53. [PubMed]
123. Lee J, Parish CL, Tomas D, Horne MK. Chronic cocaine administration reduces striatal dopamine terminal density and striatal dopamine release which leads to drug-seeking behaviour. Neuroscience. 2011 Feb;174:143–50. [PubMed]
124. Wang G-J, Volkow N, Thanos P, Fowler J. Imaging of brain dopamine pathways: implications for understanding obesity. Journal of addiction medicine. 2009;3:8–18. [PMC free article] [PubMed]
125. Stice E, Yokum S, Blum K, Bohon C. Weight gain is associated with reduced striatal response to palatable food. J Neurosci. 2010 Sep 29;30:13105–9. [PMC free article] [PubMed]
126. Stice E, Spoor S, Bohon C, Small DM. Relation between obesity and blunted striatal response to food is moderated by TaqIA A1 allele. Science. 2008 Oct;322:449–52. [PMC free article] [PubMed]
127. DelParigi A, Chen K, Salbe AD, Hill JO, Wing RR, Reiman EM, Tataranni PA. Persistence of abnormal neural responses to a meal in postobese individuals. Int J Obes Relat Metab Disord. 2004 Mar;28:370–7. [PubMed]
128. Stice E, Spoor S, Ng J, Zald DH. Relation of obesity to consummatory and anticipatory food reward. Physiology & Behavior. 2009;97:551–60. [PMC free article] [PubMed]
129. Volkow ND, Wang GJ, Fowler JS, Tomasi D, Baler R. Food and Drug Reward: Overlapping Circuits in Human Obesity and Addiction. Curr Top Behav Neurosci. 2011 Oct; [PubMed]
130. Fortuna JL. The obesity epidemic and food addiction: clinical similarities to drug dependence. J Psychoactive Drugs. 2012 Jan-Mar;44:56–63. [PubMed]
131. Davidson TL, Monnot A, Neal AU, Martin AA, Horton JJ, Zheng W. The effects of a high-energy diet on hippocampal-dependent discrimination performance and blood-brain barrier integrity differ for diet-induced obese and diet-resistant rats. Physiol Behav. 2012 Aug;107:26–33. [PMC free article] [PubMed]
132. Goldstone AP, Prechtl de Hernandez CG, Beaver JD, Muhammed K, Croese C, Bell G, Durighel G, Hughes E, Waldman AD, et al. Fasting biases brain reward systems towards high-calorie foods. Eur J Neurosci. 2009 Oct;30:1625–35. [PubMed]
133. Chaput JP, Drapeau V, Hetherington M, Lemieux S, Provencher V, Tremblay A. Psychobiological effects observed in obese men experiencing body weight loss plateau. Depress Anxiety. 2007;24:518–21. [PubMed]
134. Rodríguez-Rodríguez E, Aparicio A, Bermejo LM, López-Sobaler AM, Ortega RM. Changes in the sensation of hunger and well-being before and after meals in overweight/obese women following two types of hypoenergetic diet. Public Health Nutr. 2009 Jan;12:44–50. [PubMed]
135. Cornier MA, Grunwald GK, Johnson SL, Bessesen DH. Effects of short-term overfeeding on hunger, satiety, and energy intake in thin and reduced-obese individuals. Appetite. 2004 Dec;43:253–9. [PubMed]
136. Gilhooly CH, Das SK, Golden JK, McCrory MA, Dallal GE, Saltzman E, Kramer FM, Roberts SB. Food cravings and energy regulation: the characteristics of craved foods and their relationship with eating behaviors and weight change during 6 months of dietary energy restriction. Int J Obes (Lond) 2007 Dec;31:1849–58. [PubMed]
137. Peckham SC, Entenman C. The influence of a hypercaloric diet on gross body and adipose tissue composition in the rat. Res Dev Tech Rep. 1962 Feb;:23. [PubMed]
138. Weiss EC, Galuska DA, Kettel Khan L, Gillespie C, Serdula MK. Weight regain in U.S. adults who experienced substantial weight loss, 1999-2002. Am J Prev Med. 2007 Jul;33:34–40. [PubMed]
139. Baskin ML, Ard J, Franklin F, Allison DB. Prevalence of obesity in the United States. Obes Rev. 2005 Feb;6:5–7. [PubMed]
140. Ochner CN, Gibson C, Shanik M, Goel V, Geliebter A. Changes in neurohormonal gut peptides following bariatric surgery. Int J Obes (Lond) 2011;35:153–66. [PMC free article] [PubMed]
141. Ochner CN, Kwok Y, Conceicao E, Pantazatos SP, Puma LM, Carnell S, Teixeira J, Hirsch J, Geliebter A. Selective reduction in neural responses to high calorie foods following gastric bypass surgery. Ann Surg. 2011 Mar;253:502–7. [PMC free article] [PubMed]
142. Ochner C, Gibson C, Carnell S, Dambkowski C, Geliebter A. The neurohormonal regulation of energy intake in relation to bariatric surgery for obesity. Physiology & Behavior. 2010;100:549–59. [PMC free article] [PubMed]
143. Bouchard C, Tremblay A, Despres JP, Nadeau A, Lupien PJ, Theriault G, Dussault J, Moorjani S, Pinault S, Fournier G. The response to long-term overfeeding in identical twins. N Engl J Med. 1990 May 24;322:1477–82. [PubMed]
144. Loos RJ, Rankinen T. Gene-diet interactions on body weight changes. J Am Diet Assoc. 2005 May;105:S29–34. [PubMed]
145. Wadden T, Brownell K, Foster G. Obesity: responding to the global epidemic. J Consult Clin Psychol. 2002;70:510–25. [PubMed]
146. Wing RR, Phelan S. Long-term weight loss maintenance. Am J Clin Nutr. 2005 Jul;82:222S–5S. [PubMed]
147. Shin AC, Berthoud HR. Obesity surgery: happy with less or eternally hungry? Trends Endocrinol Metab. 2013 Feb;24:101–8. [PMC free article] [PubMed]
148. Laferrére B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, Kovack B, Bawa B, Koshy N, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008 Jul;93:2479–85. [PMC free article] [PubMed]
149. Ochner CN, Laferrére B, Afifi L, Atalayer D, Geliebter A, Teixeira J. Neural responsivity to food cues in fasted and fed states pre and post gastric bypass surgery. Neurosci Res. 2012 Oct;74:138–43. [PMC free article] [PubMed]
150. Ochner CN, Stice E, Hutchins E, Afifi L, Geliebter A, Hirsch J, Teixeira J. Relation between changes in neural responsivity and reductions in desire to eat high-calorie foods following gastric bypass surgery. Neuroscience. 2012 May;209:128–35. [PMC free article] [PubMed]
151. Bryant EJ, King NA, Falkén Y, Hellström PM, Juul Holst J, Blundell JE, Näslund E. Relationships among tonic and episodic aspects of motivation to eat, gut peptides, and weight before and after bariatric surgery. Surg Obes Relat Dis. 2012 Oct; [PubMed]
152. Laferrére B, Reilly D, Arias S, Swerdlow N, Gorroochurn P, Bawa B, Bose M, Teixeira J, Stevens RD, et al. Differential metabolic impact of gastric bypass surgery versus dietary intervention in obese diabetic subjects despite identical weight loss. Sci Transl Med. 2011 Apr;3:80re2. [PMC free article] [PubMed]
153. Shin AC, Berthoud HR. Food reward functions as affected by obesity and bariatric surgery. Int J Obes (Lond) 2011 Sep;35(Suppl 3):S40–4. [PMC free article] [PubMed]
154. Maclean PS, Bergouignan A, Cornier MA, Jackman MR. Biology’s response to dieting: the impetus for weight regain. Am J Physiol Regul Integr Comp Physiol. 2011 Sep;301:R581–600. [PMC free article] [PubMed]
155. Freedman DS, Khan LK, Serdula MK, Dietz WH, Srinivasan SR, Berenson GS. The relation of childhood BMI to adult adiposity: the Bogalusa Heart Study. Pediatrics. 2005 Jan;115:22–7. [PubMed]
Jun 15, 2017 DietHobby: A Digital Scrapbook. 1500+ articles and 300+ videos in DietHobby reflect my personal experience in weight-loss and maintenance. One-size-doesn't-fit-all, and I address many ways of eating whenever they become interesting or applicable to me.
May 01, 2017 DietHobby is now more Mobile-Friendly. Technical changes! It is now easier to view DietHobby on iPhones and other mobile devices.
Jan 01, 2017 DietHobby is my Personal Blog Website. DietHobby sells nothing; posts no advertisements; accepts no contributions. It does not recommend or endorse any specific diets, ways-of-eating, lifestyles, supplements, foods, products, activities, or memberships.