【Full text】

The conventional prescription that people with obesity should “eat less and exercise more” remains widely used as a standard approach to weight management, despite repeated reports of its low long-term success rate [1].

At the same time, recent findings from genetics, epidemiology, physiology, and related fields have increasingly shown that body weight and body fat are biologically regulated within a certain range. These findings are helping to establish a biological framework that may explain why long-term success with weight-loss dieting is so difficult to achieve.

Following weight loss, adaptive responses are triggered through coordinated changes in metabolism, neuroendocrine function, autonomic nervous system activity, and even behavior. These responses have been shown to resist the maintenance of weight loss [4].

In this article, I will briefly introduce the biological mechanisms that may promote post-weight-loss weight rebound—or, in some cases, further weight gain. I will also explain how these mechanisms relate to, and differ from, my proposed “intestinal starvation” theory.

【Related Article】
The Spread of Dieting May Be Fueling the Rise in Obesity

Energy restriction is associated with a reduction in resting energy expenditure (REE) [5]. Many studies have reported that behavioral weight loss leads to a greater decrease in both resting and total energy expenditure than would be predicted based on changes in body composition and the thermic effect of food [4,6]. 

However, regarding the timing of its onset, the evidence is inconsistent [9]. Some studies have detected adaptive thermogenesis (AT) within a week of energy restriction, which has been associated with rapid declines in insulin secretion, depletion of glycogen stores, and loss of intracellular and extracellular fluid [10].

In contrast, a growing body of evidence suggests that underfeeding-associated AT takes weeks to develop, in association with reduced leptin secretion following the loss of body fat, among other physiological adaptations [9,11,12].

   
Although the persistence of AT also remains a subject of debate [7], some studies indicate that this metabolic adaptation may continue for years even after energy balance has been reestablished at a lower weight [13]. 
       

A number of hormones secreted from the gastrointestinal tract and adipose tissue are known to play key roles in regulating appetite, food intake, energy expenditure, and body weight [14,15].

     
Leptin is a hormone secreted by fat cells that helps regulate body weight by suppressing appetite and influencing energy expenditure. High leptin levels signal to the brain that energy stores are sufficient, whereas low leptin levels indicate that energy stores are low [16].

It has been shown that leptin levels drop within 24 hours of energy restriction [17]. Interestingly, many studies have reported a greater reduction in leptin levels than would be expected based on the loss of body fat [18,19].

It has been suggested that the primary role of leptin may be the prevention of starvation, rather than weight regulation per se [15,20]. When leptin levels fall below a certain threshold—the point at which specific physiological responses are triggered (Note1)—starvation defense mechanisms are activated, even if substantial fat stores remain [17]. This leads to a reduction in metabolic rate and physical activity, as well as an increase in hunger [21,22].

       
Furthermore, in individuals who have lost weight, an increase in the appetite-stimulating hormone ghrelin, along with decreases in the post-meal satiety signals peptide YY (PYY) and cholecystokinin (CCK), has been observed [23]. As a result, diet-induced weight loss may simultaneously reduce satiety and increase hunger, potentially promoting overeating [15].

Note 1: It has been suggested that this threshold rises as fat mass increases [17].

Food reward refers to the brain's reward response to food, which generates pleasure and satisfaction from eating, as well as the motivation to eat again. This process involves activation of the brain's reward circuitry, where neurotransmitters such as dopamine are released, leading to feelings of pleasure and increased appetite.

Modern neuroimaging studies using fMRI have shown that both nutritional status (e.g. hunger vs. satiety) and different food stimuli (e.g. high- vs. low-calorie foods, appetizing vs. bland foods) can alter activity in the brain's reward circuitry [27–29].

Recent studies in healthy individuals indicate that short- or long-term caloric restriction, as well as fasting, may increase the reward value of food—especially high-calorie, palatable foods [27,30].

These findings may help explain why calorie-restricted diets often fail in the long term [28,30].

Food addiction: similarities and differences from drug addiction

While drugs and food share certain characteristics, they also differ in important ways.

Drugs of abuse, such as cocaine, act directly on the brain's dopamine circuitry, whereas food influences these circuits more indirectly. Signals from taste and smell, nutrient sensors in the digestive tract [31], and hormones released during digestion and nutrient absorption all communicate with the brain, thereby influencing the dopamine system [25].

Food intake is primarily regulated by three interacting neural systems: the homeostatic, reward-related, and inhibitory systems [15].

The inhibitory system—mainly involving the brain region responsible for self-control and decision-making—helps regulate eating behavior and inhibit excessive food intake [34].

Cognitive control of food reward

In humans, the urge to seek and consume palatable foods can be moderated by executive functions—the cognitive processes involved in self-control and decision-making.

One of the central dilemmas in daily life is balancing one's internal goals (e.g. cutting back on sweets to maintain health and weight control) against the immediate reward of eating tempting foods. This conflict is particularly challenging when highly desirable foods, such as donuts or pizza, are readily available [25].

Prospective studies in young individuals, as well as rodent experiments, suggest that severe caloric restriction, characterized by 24-hour fasting or fat-free diets, may increase the risk of developing binge eating and bulimia in the future [37,38].

Weight-loss dieting may reduce the size, but not the number, of fat cells [39]. It remains unclear whether hyperplasia (an increase in adipocyte number) contributes to weight rebound in weight-suppressed individuals [15]. However, in a study of obese rats, adipocyte hyperplasia was observed following refeeding after fasting [40].

In humans, a similar possibility has been suggested.

The mechanisms described in Sections (1)–(5) are generally thought to represent a series of anti-starvation (or anti-weight-loss) responses (Note 2) that occur in association with energy restriction and weight loss [15].

In contrast, my intestinal starvation hypothesis proposes that when all ingested food is completely digested and no undigested matter remains in the intestinal tract, the body may interpret this condition as a starvation signal.

Intestinal starvation may occur not only during strict dietary restriction for weight loss (e.g. skipping meals or eating extremely small amounts of food), but also during more moderate dieting or even everyday eating habits that are not intended for weight loss, such as skipping breakfast, eating a light lunch, having dinner late at night, or eating only two meals a day.

Furthermore, in my intestinal starvation hypothesis, adaptive responses to intestinal starvation may lead to weight gain suggestive of an upward shift in the body-weight set point. This weight gain may involve not only body fat but also lean body mass, including skeletal muscle. Therefore, this mechanism may differ from conventional models of obesity, in which weight gain is explained primarily by an increase in body fat.

【Related article】
How Intestinal Starvation Can Lead to Weight Gain

Note ２: Because these responses are activated despite adequate energy stores, some researchers prefer the term “anti-weight-loss” rather than anti-starvation mechanisms [15].

At present, the causal relationship between the biological responses described in Sections (1)–(5) and post-weight-loss weight rebound has not yet been fully established [15]. Nevertheless, many people who have experienced weight rebound after dieting may find that these mechanisms are consistent with their own experiences.

Some researchers have pointed out that the biological forces that resist weight loss and promote the recovery of lost weight are extremely powerful and difficult to overcome for most individuals attempting to lose weight through behavioral interventions. They have also suggested that achieving long-term weight loss will require the development of interventions that weaken these biological responses themselves [15].

　　　
I generally agree with this perspective, although my approach differs somewhat. 

In my opinion, achieving long-term weight loss depends not only on developing interventions that weaken these biological responses, but also on adopting dietary and lifestyle habits that minimize activation of the body's anti-starvation (or anti-weight-loss) mechanisms in the first place. 

Maintaining this type of dietary pattern may help prolong satiety and reduce feelings of hunger. Over the long term, I propose that it may also facilitate the transmission, via the gut-brain axis, of information to the brain indicating that food remains sufficiently available.

Note 2. I do not believe that foods high in fat should necessarily be avoided. Depending on the overall composition of the diet and how such foods are consumed, they can be incorporated appropriately.

　　　
【Related Article】
Weight Loss Without Rebounding Requires Two Steps

<References>
[1] Bacon L, Aphramor L. Weight science: evaluating the evidence for a paradigm shift. Nutr J. 2011 Jan 24;10:9. 

[2-3] Deleted

[4] Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes (Lond). 2010 Oct;34 Suppl 1(0 1):S47-55. 

[5]Jiménez Jaime T et al. Effect of calorie restriction on energy expenditure in overweight and obese adult women. Nutr Hosp. 2015 Jun 1;31(6):2428-36. 

[6]Johannsen DL et al. Metabolic slowing with massive weight loss despite preservation of fat-free mass. J Clin Endocrinol Metab. 2012 Jul;97(7):2489-96. 

[7]Hall KD, Guo J. Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Gastroenterology. 2017 May;152(7):1718-1727.e3. 

[8]Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar 9;332(10):621-8. 

[9]Egan AM, Collins AL. Dynamic changes in energy expenditure in response to underfeeding: a review. Proc Nutr Soc. 2022 May;81(2):199-212. 

[10]Heinitz S et al. Early adaptive thermogenesis is a determinant of weight loss after six weeks of caloric restriction in overweight subjects. Metabolism. 2020 Sep;110:154303. 

[11] Dulloo AG, Seydoux J, Jacquet J. Adaptive thermogenesis and uncoupling proteins: a reappraisal of their roles in fat metabolism and energy balance. Physiol Behav. 2004 Dec 30;83(4):587-602. 

[12]Müller MJ, Enderle J, Bosy-Westphal A. Changes in Energy Expenditure with Weight Gain and Weight Loss in Humans. Curr Obes Rep. 2016 Dec;5(4):413-423. 

[13]Fothergill E et al. Persistent metabolic adaptation 6 years after "The Biggest Loser" competition. Obesity (Silver Spring). 2016 Aug;24(8):1612-9. 

[14]Schwartz MW et al. Central nervous system control of food intake. Nature. 2000 Apr 6;404(6778):661-71. 

[15]Ochner CN et al. Biological mechanisms that promote weight regain following weight loss in obese humans. Physiol Behav. 2013 Aug 15;120:106-13. 

[16]Hebebrand J et al. The role of hypoleptinemia in the psychological and behavioral adaptation to starvation: Implications for anorexia nervosa. Neurosci Biobehav Rev. 2022 Oct;141:104807. 

[17]Leibel RL. The role of leptin in the control of body weight. Nutr Rev. 2002 Oct;60(10 Pt 2):S15-9; discussion S68-84, 85-7. 

[18]Löfgren P et al. 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(11):6207-13. 

[19]Rosenbaum M et al. Effects of weight change on plasma leptin concentrations and energy expenditure. J Clin Endocrinol Metab. 1997 Nov;82(11):3647-54. 

[20]Ahima RS et al. Role of leptin in the neuroendocrine response to fasting. Nature. 1996 Jul 18;382(6588):250-2. 

[21] Rosenbaum M et al. Energy intake in weight-reduced humans. Brain Res. 2010 Sep 2;1350:95-102. 

[22]Kissileff HR et al. Leptin reverses declines in satiation in weight-reduced obese humans. Am J Clin Nutr. 2012 Feb;95(2):309-17. 

[23] Sumithran P et al. Long-term persistence of hormonal adaptations to weight loss. N Engl J Med. 2011 Oct 27;365(17):1597-604. 

[24]Chaptini L, Peikin S. Neuroendocrine regulation of food intake. Curr Opin Gastroenterol. 2008 Mar;24(2):223-9. 

[25]Alonso-Alonso M et al. Food reward system: current perspectives and future research needs. Nutr Rev. 2015 May;73(5):296-307. 

[26]Begg DP, Woods SC. The endocrinology of food intake. Nat Rev Endocrinol. 2013 Oct;9(10):584-97. 

[27]Goldstone AP et al. Fasting biases brain reward systems towards high-calorie foods. Eur J Neurosci. 2009 Oct;30(8):1625-35. 

[28]Siep N et al. Hunger is the best spice: an fMRI study of the effects of attention, hunger and calorie content on food reward processing in the amygdala and orbitofrontal cortex. Behav Brain Res. 2009 Mar 2;198(1):149-58. 

[29]Haase L, Cerf-Ducastel B, Murphy C. Cortical activation in response to pure taste stimuli during the physiological states of hunger and satiety. Neuroimage. 2009 Feb 1;44(3):1008-21. 

[30] Stice E, Burger K, Yokum S. Caloric deprivation increases responsivity of attention and reward brain regions to intake, anticipated intake, and images of palatable foods. Neuroimage. 2013 Feb 15;67:322-30. 

[31] de Araujo IE et al. Food reward in the absence of taste receptor signaling. Neuron. 2008 Mar 27;57(6):930-41. 

[32]Avena NM, Rada P, Hoebel BG. Sugar and fat bingeing have notable differences in addictive-like behavior. J Nutr. 2009 Mar;139(3):623-8. 

[33]Berthoud HR, Zheng H, Shin AC. Food reward in the obese and after weight loss induced by calorie restriction and bariatric surgery. Ann N Y Acad Sci. 2012 Aug;1264(1):36-48. 

[34]Pannacciulli N et al. Less activation of the left dorsolateral prefrontal cortex in response to a meal: a feature of obesity. Am J Clin Nutr. 2006 Oct;84(4):725-31. 

[35]DelParigi A et al. Successful dieters have increased neural activity in cortical areas involved in the control of behavior. Int J Obes (Lond). 2007 Mar;31(3):440-8. 

[36]Burger KS, 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. 2011 Mar 1;55(1):233-9. 

[37]Stice E, Davis K, Miller NP, Marti CN. Fasting increases risk for onset of binge eating and bulimic pathology: a 5-year prospective study. J Abnorm Psychol. 2008 Nov;117(4):941-6. 

[38]Ogawa R et al. Chronic food restriction and reduced dietary fat: risk factors for bouts of overeating. Physiol Behav. 2005 Nov 15;86(4):578-85. 

[39]Gurr MI et al. 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(5):419-36. PMID: 7174187.

[40]Yang MU, Presta E, Björntorp P. Refeeding after fasting in rats: effects of duration of starvation and refeeding on food efficiency in diet-induced obesity. Am J Clin Nutr. 1990 Jun;51(6):970-8. 

[41]Arner P. Control of lipolysis and its relevance to development of obesity in man. Diabetes Metab Rev. 1988 Aug;4(5):507-15. PMID: 3061758.

[42]MacLean PS et al. The role for adipose tissue in weight regain after weight loss. Obes Rev. 2015 Feb;16 Suppl 1(Suppl 1):45-54.

[43]MacLean PS et al. 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(6):R1577-88.

【 Full text 】

I view the human body as possessing a homeostatic system that attempts to maintain body weight within a certain range, and from this perspective, I believe that the concept of a body-weight set point carries important implications.

In this article, I will discuss the background and challenges of set-point theory, which has received renewed attention in recent years. I believe that understanding the environmental and behavioral factors that may contribute to upward shifts in the body-weight set point is important for addressing the growing problem of obesity.

Obesity and weight loss attempts

♦An obese individual who insists that a lean friend has consistently eaten more than the fat person does, may well be telling the truth.（*snip*）

The group of obese patients who are greatly in need of our understanding are those who keep to a calorie intake of perhaps 1,000 kcal per day, yet lose less than one kg per week. There is no doubt whatsoever that such people exist, and can be studied in a metabolic ward under conditions where 'cheating' is virtually impossible without being detected.

Usually these are middle-aged women who have been perhaps 40 kg overweight, and who have already lost about 20 kg. They are often depressed, hypothermic, and have a low metabolic rate. The nature of this metabolic adaptation to a low-calorie diet is not known (as of 1973), but it is a phenomenon  that has been recognized since before the 1920s (J S Garrow, 1973)[1].　

     
♦For obese individuals, a certain amount of weight loss is possible through a range of treatments, but long-term maintenance of weight loss is much more challenging, and in most cases, the weight is regained [2]. In a meta-analysis of 29 long-term weight loss studies, more than half of the lost weight was regained within two years, and by five years, more than 80% of lost weight was regained [3,4].

In addition, studies of those who are successful at sustained weight loss indicate that the maintenance of reduced body fat will probably require close attention to energy intake and expenditure, perhaps for life [5].

Contrary to popular belief, people with obesity generally have a higher absolute REE compared to leaner subjects. This is because obesity increases both body fat and metabolically active fat-free mass [7,8].

PAEE can be subdivided into "voluntary exercise" and “activities of daily living.” Despite typically engaging in less physical activity, obese individuals often have a daily energy cost for physical activity similar to that of non-obese individuals since PAEE is proportional to body weight [7,9]. Additionally, due to greater food intake, their DIT also tends to be higher [7].

Dynamic changes in energy expenditure

♦Obesity prevention is often erroneously described as a simple bookkeeping matter of balancing caloric intake and expenditure [10].

In this model, energy intake and expenditure are considered independent parameters determined solely by behavior. It is assumed that an obese person can steadily lose weight by eating less and/or moving more at a rate of one pound for every 3,500 kcal (or one kg for every 7,200 kcal) of accumulated dietary caloric deficit [7,11]. This view has been referred to as a “static model” of weight loss, but it has been shown to be physiologically impossible [7,12]. 

Body weight set point theory

♦In recent years, the influence of homeostatic control has become increasingly recognized, and growing evidence suggests that the body employs physiological mechanisms to regulate energy balance and maintain body weight around a genetically and environmentally determined set point [12].

In 1953, Kennedy proposed that body fat storage is regulated [15]. In 1982, nutritional researchers William Bennett and Joel Gurin expanded on Kennedy's concept when they developed the set-point theory [16]. The model has been widely adopted, and strengthened particularly after the discovery of leptin in the 1990s [7,12].

When an individual loses weight, the body significantly reduces energy expenditure to a degree that is often greater than predicted based on changes in body composition or the thermic effect of food. This process also causes an increase in appetite through hormonal regulation and alters food preferences through behavioral changes, to drive body weight back toward its set-point range[7,16]. 

♦Maintenance of a 10% or greater reduction in body weight in lean or obese individuals is accompanied by about 20 to 25% decline in 24-hour energy expenditure.  This decrease in weight maintenance calories is 10–15% greater than predicted based solely on changes in fat and lean mass [17,18].

Since obese individuals also display these compensatory metabolic adjustments in response to dietary restriction, obesity may be considered a natural physiological state for some people. Experimental studies on obesity in animals similarly suggest a view of obesity as a condition of body energy regulation at an elevated set point [19]. 

♦A meta-analysis of cross-sectional studies investigating adaptive thermogenesis (AT) by comparing formerly obese subjects who had lost weight with BMI-matched subjects who were never obese, found a 3–5% lower resting energy expenditure (REE) in formerly obese subjects compared to never obese controls [20].

This effect means, for example, that if an obese woman reduced her weight from 100 kg to 70 kg, she would have to consume fewer calories to remain at 70 kg than a woman who had consistently weighed 70 kg [6]. Similar results have been confirmed in animal experiments involving obese and normal-weight rats.

This suggests that the frequent claim made by obese people that they eat the same or less than their lean friends but lose no weight, must be given more credence than it is ordinarily accorded [19].

♦In addition, hyperphagia (overeating) has been demonstrated following experimental semi-starvation and short-term underfeeding, which is probably the result of homeostatic signals resulting from the loss of both body fat and lean tissue [7,21].

　
♦This theory also suggests that a person's body-weight set point is established early in life and remains relatively stable unless altered by specific conditions. However, the set point may change throughout one’s life due to factors such as marriage, childbirth, menopause, aging, and disease [16]. 

On the other hand, the set-point theory remains hypothetical because the molecular mechanisms involved in set-point regulation have not yet been fully elucidated, and some researchers may consider the theory overly simplistic [16].

On the other hand, some researchers have pointed out important limitations of the body-weight set-point model. 

If a homeostatic system truly exists to maintain body weight within a certain range, a fundamental question arises: why do so many individuals in Western countries continue to gain weight gradually throughout majority of their adult lives? In particular, this model does not adequately explain the increasing prevalence of obesity observed in many societies worldwide since around the 1970s [22].

　　
In response, some researchers have suggested that while metabolic resistance to sustaining a reduced body weight is strong, metabolic resistance to sustained increased adiposity may not be physiologically long-lasting. Indeed, the steady increase in obesity prevalence supports the idea that the human body may be physiologically more permissive of weight gain than of weight loss [17,23]. 

These explanations that continuous consumption of high-calorie diet leads to an increase in the body-weight set point may sound plausible at first. However, in my opinion, if body weight changes in only one direction in response to a single external factor, it can no longer be considered a true “set point.”

Moreover, when this hypothesis is applied to humans, it fails to account for the fact that some individuals remain lean despite frequently consuming similarly high-calorie foods. In practice, several contradictions can be identified, including the following: 

I propose that upward shifts in the body-weight set point are associated with adaptive responses to intestinal starvation.
The next section provides a more detailed explanation of this mechanism. 

At present, many international organizations classify obesity as a chronic disease.

Some researchers interested in the body-weight set-point theory have argued that determining whether obesity, as a chronic condition, is treatable requires a clear understanding of how genetic and environmental factors interact to regulate the set point. At the same time, it is also true that many important environmental and social influences remain insufficiently explained [22].

In this article, I will introduce the concept of “intestinal starvation” as a complementary perspective to address these challenges. The key points are outlined below in four parts.

It is generally assumed that weight gain requires a positive energy balance, and the recent rise in obesity is often explained by increased consumption of high-calorie foods and reduced levels of physical activity. Paradoxically, however, the fact that obesity rates have increased in parallel with the growing prevalence of dieting aimed at weight loss [30] suggests that our current understanding of energy balance may warrant reconsideration [12].

What I want to emphasize is that while short-term weight gain due to overeating can be explained by excess energy intake, long-term and potentially irreversible weight gain may instead be triggered by energy deprivation or by the body’s perception that food is scarce. This pattern is also consistent with the phenomenon in which body weight increases beyond its previous level following experimental starvation or weight-loss dieting. 

【Related Articles】The Spread of Dieting May Be Fueling the Rise in Obesity

It is certainly true that high-calorie foods have become increasingly common since the 1970s. However, an even more important factor affecting the human body may be the rise of food processing—particularly ultra-processing. As food processing advanced, hard-to-digest components were gradually removed, while softer and more easily digestible components became increasingly dominant. 

Intestinal starvation is a physiological state that is more likely to occur when four factors overlap simultaneously. This concept provides a framework for understanding obesity as a chronic condition arising from interactions between genetic and environmental factors.

【Related Article】Three (+1) Factors That Accelerate “Intestinal Starvation”

In cases of weight gain that may reflect an upward shift in the body-weight set point through intestinal starvation, the overall efficiency of nutrient absorption may increase. In other words, from the perspective of energy homeostasis, the balance point at which energy intake and expenditure are matched may itself shift to a higher level. This perspective may help explain why even obese individuals with substantial body fat often exhibit compensatory metabolic responses to caloric restriction.

【Related Article】How Intestinal Starvation Can Lead to Weight Gain
      

As mentioned in the section 2, an animal study in rats reported that 90 days of exposure to a “high-energy diet” resulted in irreversible weight gain suggestive of an upward shift in the body-weight set point (Rolls et al., 1980). However, the “fattening diet” used in this experiment consisted mainly of commercially available, highly palatable foods such as potato chips, cheese crackers, and cookies [25]. At the same time, these foods were also highly refined carbohydrates and (ultra-)processed foods.

In contrast, the solid chow provided to the control group consisted of cracked grains, soybean meal, fish meal, and similar ingredients, and may have contained larger amounts of less digestible matter, such as dietary fiber and the tough cell walls of plants. In this respect, the composition of the control diet may have resembled that of human diets commonly seen more than 50 years ago. 

         
Therefore, I believe that caution is needed before concluding that the long-term consumption of a high-energy diet directly caused weight gain suggestive of an upward shift in the body-weight set point.
            

<References>

[1]Garrow JS. Diet and obesity. Proc R Soc Med. 1973 Jul;66(7):642-4. PMID: 4741395; PMCID: PMC1645095.

[2]Wu T, Gao X, Chen M, van Dam RM. Long-term effectiveness of diet-plus-exercise interventions vs. diet-only interventions for weight loss: a meta-analysis. Obes Rev. 2009;10(3):313–323. 

[3] Hall KD, Kahan S. Maintenance of Lost Weight and Long-Term Management of Obesity. Med Clin North Am. 2018 Jan;102(1):183-197. 

[4]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(5):579-84. 

[5]Wing RR, Hill JO. Successful weight loss maintenance. Annu Rev Nutr. 2001;21:323-41. 

[6]Jou C. The biology and genetics of obesity--a century of inquiries. N Engl J Med. 2014 May 15;370(20):1874-7. 

[7]Hall KD, Guo J. Obesity Energetics: Body Weight Regulation and the Effects of Diet Composition. Gastroenterology. 2017 May;152(7):1718-1727.e3. 

[8]Nelson KM, Weinsier RL, Long CL, et al. Prediction of resting energy expenditure from fat-free mass and fat mass. Am J Clin Nutr. 1992;56:848–856.

[9]Westerterp KR. Physical activity, food intake, and body weight regulation: insights from doubly labeled water studies. Nutr Rev. 2010;68:148–154.

[10] Levine DI. The curious history of the calorie in U.S. policy: a tradition of unfulfilled promises. Am J Prev Med. 2017;52:125–129.

[11] Hall KD, Chow CC. Why is the 3500 kcal per pound weight loss rule wrong? Int J Obes (Lond). 2013 Dec;37(12):1614. 

[12] Egan AM, Collins AL. Dynamic changes in energy expenditure in response to underfeeding: a review. Proc Nutr Soc. 2022 May;81(2):199-212. doi: 10.1017/S0029665121003669. Epub 2021 Oct 4. PMID: 35103583.

[13]Thomas DM, Martin CK, Lettieri S et al. (2013) Can a weight loss of one pound a week be achieved with a 3500-kcal deficit? Commentary on a commonly accepted rule. In Int J Obes 37, 1611–1613.)

[14]Hall KD, Heymsfield SB, Kemnitz JW et al. Energy balance and its components: implications for body weight regulation. Am J Clin Nutr. 2012 Apr;95(4):989-94. 

[15]KENNEDY GC. The role of depot fat in the hypothalamic control of food intake in the rat. Proc R Soc Lond B Biol Sci. 1953 Jan 15;140(901):578-96. 

[16] Ganipisetti VM, Bollimunta P. Obesity and Set-Point Theory. 2023 Apr 25. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 37276312.

[17] Rosenbaum M, Leibel RL. Adaptive thermogenesis in humans. Int J Obes (Lond). 2010 Oct;34 Suppl 1(0 1):S47-55. 

[18] Leibel R, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Eng J Med. 1995;332:621–28.

[19] Richard E. Keesey, Matt D. Hirvonen, Body Weight Set-Points: Determination and Adjustment, The Journal of Nutrition, Volume 127, Issue 9, 1997, Pages 1875S-1883S, ISSN 0022-3166.

[20]Astrup A, Gøtzsche PC, van de Werken K, et al. Meta-analysis of resting metabolic rate in formerly obese subjects. Am J Clin Nutr. 1999 Jun;69(6):1117-22.

[21] Dulloo AG, Jacquet J, Girardier L. Poststarvation hyperphagia and body fat overshooting in humans: a role for feedback signals from lean and fat tissues. Am J Clin Nutr. 1997;65:717–723.

[22]Speakman JR, Levitsky DA, Allison DB, 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(6):733-45. 

[23] Schwartz MW, Woods SC, Seeley RJ, et al. Is the energy homeostasis system inherently biased toward weight gain? Diabetes. 2003 Feb;52(2):232-8. 

[24] Corbett SW, Stern JS, Keesey RE. Energy expenditure in rats with diet-induced obesity. Am J Clin Nutr. 1986 Aug;44(2):173-80.

[25] Rolls B.J., Rowe E.A., Turner R.C. Persistent obesity in rats following a period of consumption of a mixed high energy diet. J Physiol. 1980 Jan;298:415-27. 

[26](Deleted)

[27] Dykes J et al. Socioeconomic gradient in body size and obesity among women: the role of dietary restraint, disinhibition and hunger in the Whitehall II study. International Journal of Obesity 2004 Feb,:262-68.

[28] Poskitt EM. Countries in transition: underweight to obesity non-stop? Ann Trop Paediatr. 2009 Mar;29(1):1-11.

[29] Gary Taubes. 2011. Why we get fat. New York: Anchor Books. Pages 15-32.

[30] Montani JP, Schutz Y, Dulloo AG. Dieting and weight cycling as risk factors for cardiometabolic diseases: who is really at risk? Obes Rev. 2015 Feb;16 Suppl 1:7-18.
      

【Full text】

Until the 1960s, obesity was widely attributed primarily to “overeating” and a “lack of willpower,” and relatively little research focused on the biology of obesity itself. However, this view was significantly influenced by overfeeding experiments conducted by Professor Ethan Sims and his colleagues in the late 1960s [1].

Subsequent reports indicated that the overfeeding experiment lasted about 200 days and that the 20 participants gained an average of about 9–11 kg. However, when their energy intake returned to normal levels after the experiment, most participants returned to near their original weight over the following weeks and months. Only two were reported to have maintained the weight they had gained [2,3].

These overfeeding experiments showed that weight gained through short-term overfeeding is not necessarily easy to maintain over the long term. Furthermore, they suggest that biological factors not fully explained by energy intake alone may be involved in the development and maintenance of obesity [1].

■In 1990, researchers at Laval University conducted an overfeeding study involving 12 pairs of sedentary male identical twins. Each participant's daily energy requirements were measured before the experiment, after which they consumed an additional 1,000 kcal per day over a 100-day period (six days per week, for a total of 84 days). The participants lived in a university dormitory and were under staff supervision 24 hours a day [4].

On average, body weight increased by 8.1 kg, of which 5.4 kg (approximately 67%) was body fat. However, there was substantial individual variation in weight gain, ranging from 4.3 to 13.3 kg [4].

■Leaf and Antonio reviewed overfeeding studies conducted up to 2017 that reported changes in body weight and body composition. They identified 25 studies that reported changes in fat mass (FM) and fat-free mass (FFM) in addition to weight gain, with study durations ranging from 9 to 100 days. With the exception of four studies, all involved populations with low levels of habitual physical activity [6]. Because the studies had different objectives, changes in body weight several months after the overfeeding period were not necessarily reported. 

The review summarized the 25 studies according to dietary composition.

Among them, 10 studies used diets relatively high in carbohydrates and fat and relatively low in protein (11–15% of total energy intake). In these studies, most of the weight gained was FM, accounting for approximately 60–70% of the total weight gain. The authors also noted that, in the absence of exercise, much of the increase in FFM may reflect increases in body water rather than skeletal muscle [6,7].

In contrast, even with a similar energy surplus, higher-protein diets were associated with less gain in FM and more favorable changes in body composition [6,8].

Energy expenditure (EE) increases with overfeeding and weight gain. This is because resting energy expenditure, diet-induced thermogenesis, and energy expenditure from physical activity all increase[9].

An increase in EE beyond what would be predicted from changes in body weight and body composition is referred to as “metabolic adaptation” [9,10].

Historically, this concept is thought to have originated from early observations that body weight did not increase as much as expected despite increased food intake. Researchers hypothesized that there might be an adaptive mechanism of energy expenditure that acts to dissipate excess energy [1,10].

Subsequent studies have made it possible to strictly control energy intake and examine the various components of EE in greater detail [10]. However, studies have produced inconsistent findings regarding the extent to which metabolic adaptation occurs in response to overfeeding [11,12,13]. 

   
    
■In 1995, Leibel et al. examined energy expenditure (EE) in 18 individuals with obesity and 23 who had never been obese after their body weight was reduced by 10–20% below their usual weight or increased by 10% through overfeeding.

The study suggested that maintaining body weight below or above its usual level may induce changes in EE that oppose the change in weight, potentially acting to return body weight toward its previous  level [9].

■Johannsen et al. studied 35 young adults (mean BMI, 25.6 ± 2.3) who consumed a diet providing 40% more energy than their baseline energy requirements for eight weeks. Sleeping metabolic rate (SMR), sedentary 24-hour energy expenditure (24h-EE), and other measures were assessed before and after overfeeding.

On average, participants gained 7.5 kg (range, 2.3–10.7 kg), of which 4.2 kg—more than half—was fat. Overfeeding increased SMR, sedentary 24h-EE, and EE on average, although there was substantial individual variation in these responses [10].

During weight loss, metabolic adaptation—a reduction in EE beyond what would be expected—is observed relatively consistently. In contrast, findings are inconsistent as to whether a similar metabolic adaptation occurs during overfeeding to dissipate excess energy [10].

Some studies have reported metabolic adaptation in response to overfeeding [4,7,16], whereas others have found that much of the increase in EE can be explained by the normal increase in energy requirements associated with gains in body weight and changes in body composition [12,13,17,18]. In the study by Johannsen et al., no clear metabolic adaptation to overfeeding was observed overall, although there was substantial individual variation in the response [10].

These findings suggest that metabolic adaptation during weight loss and the EE response to overfeeding may not necessarily be symmetrical. 

As discussed above, there is substantial individual variation in how body weight and EE respond to overfeeding. However, most overfeeding experiments last only a few weeks to a few months and therefore do not fully replicate the processes underlying obesity that develops gradually over several years.

I believe this difference may be explained using the concept of a “body-weight set point.” 

For example, if a person whose weight is normally stable at 70 kg temporarily increases to 73 kg as a result of overeating, this can be viewed as a change caused by increased energy intake.

I believe that an upward shift in the body-weight set point may involve adaptive physiological responses that occur when the body perceives a state of starvation. However, this has not been directly demonstrated by overfeeding experiments; rather, it is a hypothesis proposed in this blog.

Final thoughts
What these overfeeding studies show is that although overfeeding can increase body weight, the weight gained is not necessarily maintained. Weight gain resulting from short-term overfeeding may therefore need to be distinguished from obesity as a chronic condition that develops over several years.

As Bray has pointed out, the history of these overfeeding and underfeeding studies suggests that preventing and treating obesity may require more than the traditional advice to simply “eat less and exercise more” [1].
                    

<References>
[1]Bray GA. The pain of weight gain: self-experimentation with overfeeding. Am J Clin Nutr. 2020 Jan 1;111(1):17-20. 

[2]Sims EA et al. Experimental obesity in man. Trans Assoc Am Physicians. 1968;81:153-70. PMID: 5721398. 

[3]Sims EA et al. Endocrine and metabolic effects of experimental obesity in man. Recent Prog Horm Res. 1973;29:457-96. doi: 10.1016/b978-0-12-571129-6.50016-6. PMID: 4750591.

[4]Bouchard C et al. The response to long-term overfeeding in identical twins. N Engl J Med. 1990 May 24;322(21):1477-82. 

[5] Bouchard C et al. Overfeeding in identical twins: 5-year postoverfeeding results. Metabolism. 1996 Aug;45(8):1042-50. 

[6]Leaf A, Antonio J. The Effects of Overfeeding on Body Composition: The Role of Macronutrient Composition - A Narrative Review. Int J Exerc Sci. 2017 Dec 1;10(8):1275-1296. 

[7]Norgan NG, Durnin JV. The effect of 6 weeks of overfeeding on the body weight, body composition, and energy metabolism of young men. Am J Clin Nutr. 1980 May;33(5):978-88. 

[8].Bray GA et al. Effect of protein overfeeding on energy expenditure measured in a metabolic chamber. Am J Clin Nutr. 2015 Mar;101(3):496-505. 

[9]Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995 Mar 9;332(10):621-8. 

[10]Johannsen DL et al. Metabolic adaptation is not observed after 8 weeks of overfeeding but energy expenditure variability is associated with weight recovery. Am J Clin Nutr. 2019 Oct 1;110(4):805-813. 

[11]Westerterp, K. Metabolic adaptations to over—and underfeeding—still a matter of debate?. Eur J Clin Nutr 67, 443–445 (2013). 

[12]Ravussin E et al. Short-term, mixed-diet overfeeding in man: no evidence for "luxuskonsumption". Am J Physiol. 1985 Nov;249(5 Pt 1):E470-7. 

[13]Diaz EO et al. Metabolic response to experimental overfeeding in lean and overweight healthy volunteers. Am J Clin Nutr. 1992 Oct;56(4):641-55. 

[14]Reinhardt M et al. A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction. Diabetes. 2015 Aug;64(8):2859-67. 

[15]Schlögl M et al. Energy Expenditure Responses to Fasting and Overfeeding Identify Phenotypes Associated With Weight Change. Diabetes. 2015 Nov;64(11):3680-9. 

[16] Webb P, Annis JF. Adaptation to overeating in lean and overweight men and women. Hum Nutr Clin Nutr. 1983 Mar;37(2):117-31.

[17] Forbes GB et al. Deliberate overfeeding in women and men: energy cost and composition of the weight gain. Br J Nutr. 1986 Jul;56(1):1-9. 

[18]Roberts SB et al. Energy expenditure and subsequent nutrient intakes in overfed young men. Am J Physiol. 1990 Sep;259(3 Pt 2):R461-9. 

In this article, I will discuss the central theme of this blog: why a state I call “intestinal starvation” can lead to weight gain. This idea is based on my own personal experience, which I have organized and interpreted from a physiological perspective and presented here as a hypothesis. 

When I entered university, my body weight had dropped into the 30-kilogram range. Even when I increased my food intake, my weight barely increased.

However, at one point, despite eating relatively little, my body weight suddenly increased by about five kilograms over the course of four to five days. This increase involved not only body fat but also muscle mass. Because I was underweight at the time, I strongly felt that this rapid weight gain was not a coincidence but rather the result of a distinct physiological change.

　　　
The idea presented in this article may seem counterintuitive to many readers. Nevertheless, for those who feel that weight gain cannot be fully explained by calorie balance alone, I hope this perspective offers a useful way of thinking. 

The idea that humans have evolved to store fat more efficiently in preparation for temporary food shortages or famine is one that most researchers studying obesity have likely considered at least once. However, this simple hypothesis has historically been treated with caution—or even skepticism—within the scientific community[1].

Underlying this skepticism is the common observation that people with obesity tend to have a higher energy intake, whereas individuals experiencing severe famine, such as refugees in parts of Africa, are markedly underweight due to malnutrition. From this perspective , some may raise the following counterargument: 

“If hunger leads to weight gain, then refugees in Africa should be overweight.”　

This condition can be regarded as a modern form of hunger that began to emerge primarily in developed countries around the 1970s and has since been spreading to many parts of the world.

In developed countries, diets have increasingly shifted toward the routine consumption of high-calorie, highly processed foods. In particular, when a diet is consistently dominated by rapidly digestible refined carbohydrates and (ultra-)processed foods, undigested matter does not remain in the intestinal tract for extended periods, which may create conditions that make intestinal starvation more likely to occur. 

　　　
In fact, obesity has become a serious problem even among some low-income populations worldwide[2]. What is commonly observed in these settings is not simply excessive caloric intake or high sugar consumption, but rather a poorly balanced diet heavily reliant on inexpensive refined carbohydrates and highly processed foods. 

I propose that one of the fundamental problems underlying obesity is that the body-weight set point is elevated. I further suggest that this upward shift in the set point may involve adaptive responses that are triggered when the body, in some form, perceives a state of starvation. 

In this section, I will explain the concept of intestinal starvation—one form of perceived starvation—and the process by which it may lead to weight gain, using an analogy from plant biology. (Note that the discussion here is limited to intestinal starvation and does not attempt to explain other known or unknown mechanisms involved in weight gain.)

Having said that, it should be emphasized that this does not imply that the protrusions on the intestinal folds—the villi—physically elongate. What I am proposing is not a change in the intestinal structure or function itself, but rather more superficial changes that influence absorptive efficiency.

As a result, the surface area available for contact with nutrients increases, and the effective absorptive efficiency may rise in a way that is not merely transient  but can persist thereafter.

If such a change in absorptive efficiency occurs, regardless of whether the weight gain is 0.3 kg or 3 kg, the body may transition to a state of energy homeostasis at a higher body weight within a relatively short period of time. Unlike weight gain caused by overeating, this would imply an upward shift in the body-weight set point itself.

This hypothesis may help explain, at least in part, why individuals with obesity—despite having substantial energy stores in the form of body fat—can exhibit metabolic resistance to caloric restriction[3].

【Related articles】The Increasingly Important "Set-Point" Theory of Body Weight

     
    
Taken together, I propose that one fundamental difference between obese and lean individuals may lie in how efficiently ingested food is digested and absorbed.

In Japan, people with obesity sometimes describe themselves as “having a body that gains weight even from drinking water.” Of course, drinking water alone does not lead to weight gain. However, this expression may intuitively reflect a state in which nutrient absorption efficiency is elevated in individuals with obesity.

Weight gain reflecting an elevation of the body-weight set point means, from the perspective of energy homeostasis, that the balance point at which energy intake and expenditure are matched has shifted to a higher level. In other words, a more positive energy balance becomes easier to maintain, making weight loss increasingly difficult.

Even if body weight temporarily decreases through caloric restriction, it is highly likely to rebound once the original diet is resumed.

Moreover, repeated cycles of dietary restriction may raise concerns about a gradual increase in body weight over the long term. With extreme dietary restriction, prolonged periods of hunger are common, which may make intestinal starvation more likely to occur during this process and, in turn, further elevate the set point for body weight.
       

However, these findings are primarily observational and do not demonstrate that the increase in body fat itself—or the associated increase in body weight load—directly stimulates muscle growth. 

In this hypothesis, increases in muscle mass are not attributed to mechanical loading from higher body weight. Rather, they are considered to occur alongside increases in body fat to some extent as a secondary change associated with alterations in nutritional status and the metabolic environment.
          

An increase in overall nutrient uptake shifts the body toward a more positive energy balance, while simultaneously allowing the following phenomena to occur. Since digestive enzymes and many hormones are composed of proteins (amino acids), improvements in nutritional status may lead to changes in digestive function and appetite regulation mechanisms.

In contrast, in an excessively lean state, reduced absorptive efficiency may limit the body’s ability to effectively utilize ingested nutrients, such as protein. As a result, decreases in the muscle mass that supports internal organs, together with reduced secretion of digestive enzymes, can further impair the capacity to digest and absorb food efficiently.

This creates a vicious cycle in which a negative energy balance is more easily maintained. Consequently, even when caloric intake is increased, body weight may not increase easily.

【Related articles】
After Gaining Weight, We Eat Too Much and Do Less Exercise

References

[1]Speakman JR, Elmquist JK. Obesity: an evolutionary context. Life Metab. 2022 Apr 29;1(1):10-24. 

[2]Gary Taubes. Why We Get Fat. New York: Anchor Books. 2011. Pages 15-32.

[3]Richard E. Keesey, Matt D. Hirvonen, Body Weight Set-Points: Determination and Adjustment, The Journal of Nutrition, Volume 127, Issue 9, 1997, Pages 1875S-1883S, ISSN 0022-3166.

[4]Kyle UG et al. Fat-free and fat mass percentiles in 5225 healthy subjects aged 15 to 98 years. Nutrition. 2001 Jul-Aug;17(7-8):534-41. 

[5]Heymsfield SB et al. Human body composition: advances in models and methods. Annu Rev Nutr. 1997;17:527-58. 

[6] Janssen I et al. Skeletal muscle mass and distribution in 468 men and women aged 18-88 yr. J Appl Physiol (1985). 2000 Jul;89(1):81-8. 

[7]Fornari R et al. Lean mass in obese adult subjects correlates with higher levels of vitamin D, insulin sensitivity and lower inflammation. J Endocrinol Invest. 2015 Mar;38(3):367-72. 
        

First, some people think in terms like "overeating always leads to weight gain" or "exercise causes weight loss," as shown in Figure-1. 

Exercise certainly consumes more energy, but a counter-regulatory function－that the body tries to regain energy that it has expended－should work.

In other words, exercise is essentially a force that pushes the body in the direction of gaining strength and ultimately, storing energy (weight gain) as it tries to stimulate energy circulation and re-energize the body. (In particular, it works more strongly in resistant exercises that target muscles.) 

As Dr. Briffa, the author of “Escape the Diet Trap,” says in his book, it is better to think that, "originally lean people start running marathons or playing soccer, and eventually become athletes[1].” It may be a cynical view, but I think it’s probably correct. 

They know they never gain weight even though they eat a lot, and most athletes eat three well-balanced meals, plus other nutritional supplements and snacks. 

On the other hand, there might be people who have gained 3–4 kg over the past few years because their work involves desk tasks or light physical activity, and they haven’t exercised recently. 

However, the real issue, I believe, is not the lack of exercise, but rather skipping meals, eating light meals, having an unbalanced diet relying too much on carbohydrates, or irregular eating habits.

Additionally, when athletes retire, their caloric expenditure decreases and opportunities to eat often increase, which can lead to a few kilograms of weight gain. I see this as the same mechanism that causes weight to rebound after dieting, where the body returns to its set-point weight. 

However, if there is a weight gain of more than ten kilograms over a few years, this is likely due more to changes in eating habits, as explained above, and can be attributed to weight gain caused by intestinal starvation.
            

Fighters and sumo wrestlers exercise, of course, but due to the nature of their sports, they sometimes need to increase their muscle mass or body weight. However, we often hear that it’s not easy for some fighters to gain muscle mass and weight even if they eat protein supplements in addition to their three meals. 

On the other hand, those who don’t want to gain weight sometimes put on weight quite effortlessly. This is because, as I have mentioned so many times, gaining weight (meaning an increase in one’s set-point weight) requires the induction of intestinal starvation.

During high-intensity strength exercises, like barbell exercises, the body’s regulatory mechanism to restore lost energy is even more powerful than with aerobic exercise.

However, if one tries to consume more calories and nutrients every 4 to 5 hours through meals or protein supplements, some undigested food tends to remain in the intestines throughout the day, which could ultimately hinder an increase in set-point weight. 

<A sumo wrestler's diet: a practical approach to increasing body weight>
        

■For details on how weight is increased when intestinal starvation is induced, please refer to the article below. 

[Related article]
 Gaining Weight by Intestinal Starvation; What Does It Mean?

(1)The relationship between diet and exercise is not simply an energy "in/out" relationship.
Exercise is essentially a force that works toward gaining strength and weight because the opposite reaction－that the body tries to regain energy that it has expended－should work (especially in the case of high-intensity exercise).

      
(2) However, the priority is in how we control our diet. Eating three well-balanced meals every day will help undigested food to remain in the intestines, and the set-point weight is less likely to increase. 

People who are originally lean start athletics, soccer, etc., and if they eat three well-balanced meals every day, they are less likely to gain weight and maintain the same body shape over the years.

      
(3) People tend to skip meals or eat less when they aren’t exercising or are only doing light physical work. In such cases, the body's regulatory function to absorb nutrients and store fat are weaker than during exercise, but in contrast, people end up feeling hungrier and intestinal starvation is more likely to be caused, resulting in an increase in one's set-point weight. 

      
(4)The way sumo wrestlers eat and exercise is a logical approach to increasing muscle strength and body weight. By eating digestible meals including a good amount of rice twice a day, they are more likely to induce intestinal starvation. Intense training further accelerates this effect.
         

"The experts who say that we get fat because we overeat or we get fat as a  result of overeating - the vast majority  - are making the kind of mistake that would (or at least should) earn a failing grade in a high-school science class.

They're taking a law of nature that says absolutely nothing about why we get fat and a phenomenon that has to happen if we do get fat - overeating - and assuming these say all that needs to be said."
(Gary Taubes. 2011. Why we get fat. New York: Anchor Books,  Page 76.)

The way Wade explained it to me, the animal doesn't get fat because it overeats, it overeats because it's getting fat. The cause and effect are reversed.

(*snip*)

The evidence that fat tissue is carefully regulated, not just a garbage can where we dump whatever calories we don't burn, is incontrovertible.(*snip*)

Those who get fat do so because of the way their fat happens to be regulated and that a conspicuous consequence of this regulation is to cause the eating behavior (gluttony) and the physical inactivity (sloth) that we so readily assume are the actual causes."
(Taubes.  Why we get fat. Page 89-90, 93-4.)

"Just prior to the Second World War, European medical researchers argued that it is absurd to think about obesity as caused by overeating, because anything that makes people growーwhether in height or in weight, in muscle or in fatーwill make them overeat.

Children, for example, don't grow taller because they eat voraciously and consume more calories than they expend. They eat so muchーovereatーbecause they're growing."
(Taubes. Why we get fat. Page 9.)

This time, I would like to discuss three key factors－plus one additional factor－that may contribute to the occurrence of what I call “intestinal starvation."

【Related article】

In addition to these, many other factors may also be indirectly involved in the recent increase in obesity. However, it is not always clear how multiple factors combine to drive weight gain across the population as a whole.

I propose that one possible explanation involves a mechanism I refer to as “intestinal starvation.”

This condition is unlikely to occur due to a single factor alone, but is more likely to arise when the three factors (+1) described below overlap at the same time. For this reason, it may help explain how everyday eating habits and lifestyle patterns—when considered together—can lead to weight gain.

This idea is consistent with the view that consuming low-GI (glycemic index) foods and minimally processed foods help prevent obesity.

It doesn’t depend on the amount of calories you eat, but the quality and balance of food you eat. For example, eating a variety of foods and having a good balance vs a bad balance may lead to gaining weight, even if you eat small amounts.

Eating speed, how well you chew, and how much fluid you drink during meals may also influence this factor.

【Related article】
The Dilution Effect/ Pushing Out Effect of Carbohydrates

Eating Fat/Oil Can be a Deterrent to Gaining Weight (3 Perspectives Regarding Fat)

Many people report gaining weight due to lifestyle changes such as skipping breakfast or eating dinner late at night. Behind this type of weight gain caused by irregular daily routines lies the issue of long gaps between meals—in other words, enduring hunger for extended periods of time.

Eating late at night does not always lead to weight gain by itself. If dinner has to be late, having a small snack in the early evening—such as nuts, milk, or a sandwich—can help prevent intestinal starvation by avoiding prolonged hunger.

Even when eating the same meals, people with strong stomachs and high digestive capacity may be more likely to experience intestinal starvation than those whose digestion is slower. In today’s society, where energy-dense foods are common, the ability to digest protein and fat may have a particularly strong influence on whether intestinal starvation occurs.

On the other hand, people with sensitive stomachs or conditions such as gastroptosis may find it difficult to fully digest all ingested food in the first place.

If genetic factors contribute to obesity, then the secretion of enzymes and hormones that affect digestive capacity and appetite, as well as the sensitivity of their receptors, is likely to play a major role. Of course, these factors can also change due to environmental and lifestyle influences.
      

In addition to the three factors, I added one more important element as “+1,” which can be explained by “continuity.”

What this means is that not only the meal you have just finished, but also your previous meal and the meals before that can influence whether intestinal starvation occurs or not. 

The reason is that the intestines are very long—about 7 to 8 meters in total (with the small intestine alone being about 6 meters)—and it takes, on average, more than ten hours for food to pass through the entire intestinal tract. Because intestinal starvation is judged across the whole intestine (or possibly only the small intestine), it is influenced not only by a single meal, but also by your previous meal and the meals before that.

This is also the flip side of why eating well-balanced meals three times a day is thought to help prevent obesity: it helps ensure that the intestines are continuously exposed to food of adequate quality, reducing the chance that the body interprets the situation as “starvation.” 

From an evolutionary biology perspective, humans and many other animals are thought to have developed mechanisms to cope with intermittent food shortages over long periods of evolution. Because periods of abundant food were limited, the ability to store energy in the liver, skeletal muscles, and adipose tissue was likely favored by natural selection.

From this perspective, obesity can be understood not merely as a consequence of overeating, but as a state that arises as a result of adaptive physiological responses, in which the body attempts to store energy when it perceives a risk of starvation.

　
The concept of “intestinal starvation” adds a new perspective to the discussion of how our bodies perceive a lack of food, moving beyond the traditional focus on energy intake alone.

【Related articles】
Why Does the Body Perceive That It Is More Starved than in the Past?

Note 1: It is unclear whether intestinal starvation is sensed throughout the entire gut or only in the small intestine, which is sometimes referred to as the "second brain."

Note 2: Because dietary fats generally require more time for digestion and gastric emptying, they may, in some individuals, help prevent the onset of intestinal starvation. However, there is substantial individual variability in the capacity to digest fats, and when fats are consumed together with refined carbohydrates, this suppressive effect may not be sufficiently achieved.

【Related articles】Eating Fat/Oil Can be a Deterrent to Gaining Weight

Even if you consume a large amount of food, a diet composed mostly of refined carbohydrates and other easily digestible items (including certain protein sources and small amounts of fat)—combined with long gaps between meals, such as eating only twice a day—can induce an intestinal starvation state or a condition very close to it.

Even when overall food intake is small, a diet composed mainly of easily digestible foods such as refined carbohydrates and certain protein sources (e.g., ultra-processed foods such as simple burgers or sandwiches, or instant noodles) may still trigger intestinal starvation. 

Due to recent dieting trends, many people try to keep breakfast or lunch light in an effort to lose weight, but this approach may end up being counterproductive in the long run.

In contrast, when you eat a balanced diet including fiber-rich vegetables, and minimally processed foods three times a day, some fraction of undigested matter remains in the intestinal tract continuously throughout the day, making it less likely for intestinal starvation to be induced.

Since human genes are unlikely to change dramatically over just a few decades, changes in lifestyle and food environments since the 1970s are likely to have had a substantial impact on the recent global rise in obesity[3].

Strictly speaking, four factors (see Note 3) need to overlap for intestinal starvation to be triggered, which may explain why obesity is more likely to occur at the intersection of multiple factors, including genetic, environmental, and physiological factors.

Note3: The four factors are “what you eat,” duration of hunger, digestive ability, and continuity.

Genetic traits related to intestinal starvation include the secretion capacity and receptor sensitivity of enzymes and hormones that regulate digestion and appetite. In particular, differences in genetic background—reflecting both population-level and individual variability—that enable more rapid digestion of proteins and fats may influence the occurrence of intestinal starvation.

Of course, these biological traits may also change as a result of acquired conditions, such as obesity or gastric reduction surgery performed for weight loss.

Since the 1970s, one of the most notable environmental changes, I believe, has not merely been the increase in energy-dense foods, but rather the rise in easily digestible foods resulting from industrialized food production. Examples include refined carbohydrates, certain protein sources, and ultra-processed foods.

In vegetables and grains, the less digestible parts have been removed (e.g. refined grains), and some are now mashed or strained (e.g. mashed potatoes and potage soups). Meat and fish are often minced or ground, making them easier to digest.

<Lifestyle>

Intestinal starvation is related not only to what people eat but also to "how they eat."

Since the 1970s, changes in lifestyle have been accompanied by dramatic shifts in eating habits. In Japan, for example, the traditional rice-based breakfast has gradually been replaced by a Western-style breakfast consisting of toast, coffee, and fried (or boiled) eggs, etc.

    
In addition, many people now tend to eat light breakfasts and lunches, while consuming the majority of their daily calories at dinner. Such eating patterns may promote intestinal starvation, because our intestines are about seven to eight meters long, and all ingested food may be completely digested while traveling through the intestinal tract. 

Intestinal starvation represents an adaptive physiological response related to intestinal processing and hormonal secretion, and may prove that people who eat a balanced diet every day are likely to be less prone to weight gain. 

Although intestinal starvation may not be directly associated with the gut microbiota, the types of foods consumed have a significant impact on the intestinal environment.

Individuals who eat a wide variety of foods in a well-balanced manner are less likely to induce intestinal starvation, which may indirectly suggest a relationship that those with a healthier gut microbiota are less susceptible to obesity.

<References>

[1]Flores-Dorantes MT, Díaz-López YE, Gutiérrez-Aguilar R. Environment and Gene Association With Obesity and Their Impact on Neurodegenerative and Neurodevelopmental Diseases. Front Neurosci. 2020 Aug 28;14:863. 

[2]Khan MJ et al. Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature. J Obes. 2016;2016:7353642. 

[3] Jason Fung. The Obesity Code. Greystone Books, 2016, Page 21-2.

In everyday conversation, weight gain is often understood simply as “an increase in body weight (usually body fat)” compared with the past. However, this expression may lump together multiple processes that are physiologically distinct.

To make the discussion easier to follow, the complex phenomena involved in weight gain are deliberately divided here into two processes as a hypothetical framework.

     
For example, the idea that eating high-calorie foods leads to weight gain is widely shared. In contrast, understanding phenomena such as weight rebound after dieting—sometimes resulting in greater weight gain than before—requires a more explicitly physiological perspective.

I believe that because these qualitatively different processes of weight gain have often been discussed without clear distinction, misleading information about weight loss may have spread, leading many people to engage in dieting practices that are not necessarily appropriate or effective. 

【Related article】

The Increasingly Important "Set-Point" Theory of Body Weight

The first type of “weight gain” reflects, and arises as part of, the body’s homeostatic drive to return to its set point (Fig. 1A).

Many people who are overweight, or tend to gain weight easily, deliberately try to keep their body weight lower by reducing their daily caloric intake and/or increasing physical activity.

In many countries, people often talk about “holiday weight gain” or say that high-calorie foods inevitably make them gain weight. Some also claim, “I gain weight as soon as I eat a little more.”

But in most cases, these experiences can be explained by the homeostatic mechanism that pulls body weight back toward its set point—meaning that the person is simply repeating small cycles of “mini-diets” followed by “mini-rebounds.”

In contrast, the second type of “weight gain” refers to cases in which the body-weight set point itself gradually increases (Fig. 1B).

I propose that an upward shift in the body-weight set point is associated with the body’s adaptive responses to perceived starvation. Broadly speaking, the body is thought to perceive starvation through two major pathways: one is a severe energy deficit caused by excessive caloric restriction, and the other is what I describe in this blog as “intestinal starvation.”

【Related article】
Biological Responses Driving Weight Rebound After Weight Loss

    
Here, I will focus on the latter—cases in which an increase in the body-weight set point is thought to be primarily associated with intestinal starvation.

This pattern can be observed in people who are mindful of their caloric intake and keep breakfast or lunch light—such as opting for a simple burger or sandwich, or instant noodles—yet still find themselves saying, “I’ve gained three kilos over the past year,” or “I’m ten kilos heavier than I was three years ago.”

This phenomenon cannot be adequately explained by simple calorie balance alone. Rather, it suggests the possible involvement of intestinal starvation—which may be induced during prolonged periods of hunger—as well as other regulatory mechanisms in elevating the body-weight set point.

Such a shift may contribute to more fundamental differences between individuals who tend to gain weight easily and those who remain lean.

Indeed, research on set-point theory suggests that, for some individuals, obesity may represent a “natural physiological state” in which energy balance is stably maintained at a relatively high set point for body weight[1].

In real-world weight gain and post-diet rebound, the mechanism for maintaining body weight (A) and the mechanism by which the set point itself increases (B) often operate simultaneously or in an overlapping manner.

For example, the common observation that most people return to their original weight after dieting can be understood as the result of a homeostatic, weight-preserving mechanism (A) described above.

In contrast, when body weight not only returns to baseline but also exceeds the previous level, a mechanism (B) that raises the set point itself may be involved. This is because, during the process of caloric restriction, conditions may arise under which the body comes to perceive itself as being in a state of starvation.

■Sumo wrestlers in Japan are well known for eating large meals and becoming very heavy. In reality, however, their weight gain can be understood as involving a combination of mechanisms (A) and (B) described above.

<References>

[1] Richard E. Keesey, Matt D. Hirvonen, Body Weight Set-Points: Determination and Adjustment, The Journal of Nutrition, Volume 127, Issue 9, 1997, Pages 1875S-1883S, ISSN 0022-3166.

All through the year, we get thinner when we are busy, and we gain a little fat when we aren’t active and eat a lot. Although everyone repeats the same pattern, even if we don't calculate calories strictly, the body shape of person won't change so easily. Fat people are fat and thin people are thin. 

In other words, I believe that each person has a stable weight based on their body's homeostatic functions, which I initially defined as their "base weight."
     

[Base weight] = The stable weight one returns to after spending 3-5 days relaxing without excessive exercise or work, while consuming calories based on their daily energy needs.
      

Most of us do not consciously adjust our daily energy intake and expenditure. Nevertheless, an individual's body weight remains relatively stable.

Individual body weight variance is typically only 0.5% over periods of 6 to 10 weeks[1,2] (Khosha and Billewicz 1964). According to cross-sectional data, weight changes over longer periods of time are still modest, and even diabetic individuals display coefficients of body weight variation of only 3.7– 4.6% over a period of five years[1,3] (Goodner and Oglive 1974). 

With the global increase in obesity since the 1970’s, these coefficients of body weight variation may no longer be as accurate. However, many people still stay lean (especially in Asia), and, in fact, even those who are overweight or obese manage to maintain their weight, heavy as they may be, for many years[4]. 

In other words, despite some fluctuations in weight in daily life, there must be an internal regulatory mechanism that works to keep weight and fat within a certain range over the long haul.

■In recent years, the role of homeostatic regulation has been acknowledged, and there is growing evidence that the body employs physiological mechanisms to control energy balance and maintain body weight at a genetically and environmentally determined "set-point."[5]

When I started writing this blog, I had no knowledge of the theory about the body's "set-point," but it almost aligned with what I had always believed. I now believe that understanding the set-point theory is crucial in preventing the spread of obesity and proposing effective weight loss methods.

In particular, to explain the global rise in obesity since the 1970’s, I believe it is essential to understand how (I) genetic and biological factors, and (II) environmental and behavioral factors combine to increase the body’s set-point for weight. I believe my intestinal starvation theory can contribute to this understanding.

For more details, please refer to the articles below.

[Related article] 
 The Increasingly Important "Set-Point" Theory of Body Weight
      

References：
[1]Richard E. Keesey, Matt D. Hirvonen. Body Weight Set-Points: Determination and Adjustment. The Journal of Nutrition, Volume 127, Issue 9, 1997, Pages 1875S-1883S, ISSN 0022-3166.

[2]KHOSLA T, BILLEWICZ WZ. MEASUREMENT OF CHANGE IN BODY-WEIGHT. Br J Nutr. 1964;18:227-39. 

[3]Goodner CJ, Ogilvie JT. Homeostasis of body weight in a diabetes clinic population. Diabetes 1974 Apr;23(4):318-26. 

[4] Gary Taubes. 2011. Why we get fat. New York: Anchor books, Page 59.

[5]Egan AM, Collins AL. Dynamic changes in energy expenditure in response to underfeeding: a review. Proc Nutr Soc. 2022 May;81(2):199-212. doi: 10.1017/S0029665121003669. Epub 2021 Oct 4. PMID: 35103583.

[6]Ganipisetti VM, Bollimunta P. Obesity and Set-Point Theory. 2023 Apr 25. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 37276312.

[7]Bray GA.The pain of weight gain: self-experimentation with overfeeding. Am J Clin Nutr. 2020 Jan 1;111(1):17-20.