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The prescription for people with obesity to ”eat less and exercise more”remains a widely used approach to weight management, despite its well-documented failures[1]. It has been suggested that most of the weight lost through dieting is regained over the long term[2]. 

According to research in genetics, epidemiology, and physiology, body fat and body weight are known to be tightly regulated. When a person attempts to maintain weight loss, adaptive responses involving coordinated changes in metabolic, neuroendocrine, autonomic, and behavioral functions are triggered, acting to oppose the maintenance of the reduced weight[4].

In this post, I’d like to take a brief look at these biological mechanisms that may drive weight rebound and even promote further weight gain after dieting. I will also explain how my theory of intestinal starvation differs from these mechanisms.

【Related Articles】 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 effects of food[4,6].

However, regarding the timing of its onset, there is inconsistent evidence[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 intra-and extra cellular fluid[10].

In contrast, a growing body of evidence suggests that underfeeding-associated AT takes weeks to develop[11], primarily in association with reduced leptin secretion resulting from the reduction of stored fat[9,12]. 

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 through stimulation of the satiety center and by increasing energy expenditure. High leptin levels are interpreted by the brain that energy reserves are high, whereas low leptin levels indicate that energy reserves 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 for given losses of adipose tissue[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(*1)—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].

(* 1) It has been suggested that this threshold rises as fat mass increases[17].

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, behavioral weight loss can simultaneously induce a decrease in satiety and an increase in hunger, potentially promoting overeating[15].

Food reward refers to the brain’s mechanism that generates pleasure and satisfaction from eating, as well as the motivation or desire to eat again. This process involves activation of the brain’s reward circuitry, where neurotransmitters such as dopamine are released, leading to feelings of well-being 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, appetizing vs. bland foods) can alter activity in the brain’s reward circuitry[27,28,29].

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 for high-calorie, palatable items[27,30]. 

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

<Food Addiction and Its Differences from Drug Addiction>

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

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

Food intake is primarily regulated by three interactive 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 excess food intake[34].

<Cognitive control of food reward>

In humans, the urge to seek and consume palatable foods can be moderated by cognition, specifically  executive functions. 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, like donuts or pizza, are readily available[25].

Prospective studies in young individuals, as well as animal experiments in rodents, 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 with obese rats, adipocyte hyperplasia has been observed following refeeding after fasting[40].

In humans, a similar possibility has been suggested[15].

The reactions described in section 1 to 5 are thought to represent a series of anti-starvation or anti-weight loss mechanisms(* 2) triggered by glycogen depletion or a significant decrease in stored body fat[15].

In contrast, intestinal starvation does not result from a depletion of energy. While it can occur under strict dietary restrictions aimed at weight loss—such as skipping meals or eating only very small portions—it may also be triggered by more casual dieting, or lifestyle habits not directly related to dieting, such as skipping breakfast, eating light lunches, having late dinners, or eating two meals a day.
【Related article】
Defining "Intestinal Starvation": Its Relevance to the Multifactorial Model of Obesity

I also believe that when intestinal starvation is induced, it leads to overall weight gain, suggesting an increase in body’s set-point weight. This increase likely involves not only body fat but also lean tissue such as muscle mass. Therefore, it may differ from weight gain mechanisms characterized by abnormal increases in abdominal and total body fat.

(* 2) Some researchers prefer the term "anti-weight loss" mechanism rather than anti-starvation, because these responses operate despite the presence of adequate energy stores[15].

Although a direct causal relationship between the five mechanisms (section 1-5) discussed here and weight rebound has not yet been proven[15], many people who have experienced rebounding after dieting may find these explanations relatable.

Some researchers point out that “the biological forces resisting weight loss and driving weight rebound are so powerful that most individuals attempting to lose weight through behavioral interventions are unlikely to overcome them.” At the same time, they emphasize the need to develop new strategies that can weaken these biological mechanisms in order to achieve long-term weight loss[15].

In my opinion, rather than trying to overcome these powerful biological forces, what’s truly important is to avoid triggering the anti-starvation (or anti-weight loss) mechanisms in the first place.

Currently, obesity is widely believed to result from excess caloric intake and/or lack of physical activity. Consequently, the common advice is to “eat less and exercise more.” However, many people try to reduce calories by eating light meals or very small portions (e.g., a simple sandwich, a simple burger) and endure extended periods of hunger. As the findings on food reward and inhibitory systems indicate, this approach clearly ignores the body’s natural biological mechanisms.

I would rather recommend the following approach:

    
• Mainly reduce refined carbohydrates and adjust total caloric intake—but avoid extreme restrictions.

• Increase other foods, such as fiber-rich vegetables, seaweed, dairy products, minimally processed meats and fish, and nuts. In particular, emphasize foods that are harder to digest or take longer to break down (* 2).
(* 2) Even high-calorie foods like oils and nuts can be appropriate depending on how they’re consumed.

By maintaining this dietary approach, the signal that "there is sufficient food available" may be transmitted through the gut-brain axis. Sustaining satiety and reducing hunger is key.

Moreover, nutrient-sensing systems in the digestive tract and other parts of the body have also been indicated to contribute to the generation of food reward during and after a meal[43]. By chewing slowly and savoring each bite, you can gain not only the immediate reward from taste buds but also a longer-lasting sense of satisfaction that extends well beyond the end of the meal[44].

The current obesity epidemic is often described as a mismatch between our modern, food-abundant environment and biological response patterns that evolved under food-scarce conditions[44,45]. 

From this perspective, I believe that in an environment where palatable food is readily available, even extended periods of hunger in daily life may actually promote long-term increases in body fat depending on how we combine foods.
              

<References>
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