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Losing weight and keeping it off long-term is extremely challenging for most people. This difficulty is not due to a lack of willpower or motivation, but rather complex physiological processes hardwired into the human body. The body actively resists changes in weight up or down through a coordinated network of hormonal and metabolic mechanisms aimed at maintaining stability. This coordinated regulatory system acts much like a thermostat, seeking to keep body fat within a narrow set point range. When weight is lost, whether intentionally through dieting or unintentionally through illness, the body responds by powerfully increasing hunger and reducing satiety. These changes are mediated by key appetite and satiety hormones such as ghrelin, leptin, peptide YY (PYY), amylin, and cholecystokinin (CCK). To achieve lasting weight loss, it is imperative to understand and work with, rather than against, these innate biological drives favoring regain. Success requires a nuanced, physiology-based approach focused on restoring optimal hormonal balance.
The Body Fat Thermostat
The human body aims to maintain a remarkably stable level of body fat over time, resisting changes both up and down. This coordinated regulatory system works to keep body weight within a predetermined set point range.
Homeostasis and Set Point Theory
Homeostasis refers to the ability of the body to maintain stable internal conditions despite changes in the external environment. Body weight is tightly regulated by the body through homeostatic mechanisms. The body fat set point or set weight range is the weight that the body “defends” against both gains and losses. If weight drops below the set point range, compensatory mechanisms kick in to promote regain back toward the set point. These mechanisms include reduced energy expenditure and increased hunger signals. Conversely, if weight rises above the set point range, counter-regulatory processes act to promote weight loss back down toward the set point. This coordinated regulation creates a high degree of stability in body weight over long periods, similar to how a thermostat maintains a stable temperature within a room.
The Energy Balance Equation
According to the energy balance equation, body fat is determined by the difference between calories consumed (calories in) and calories burned (calories out) over time. To lose fat, calories out must exceed calories in. However, the body can dynamically adjust both sides of this equation to resist weight loss and maintain homeostasis of the set point range. If calories in are reduced to create a deficit, the body responds by reducing calories out through decreased NEAT (non-exercise activity thermogenesis) and decreased resting metabolism. These compensatory responses severely limit actual fat loss compared to expected loss based on the calculated calorie deficit.
Hunger Hormones
In addition to reducing energy expenditure, the body powerfully increases hunger signals in response to weight loss through coordinated changes in key appetite and satiety hormones. The levels of virtually all hormones acting to increase hunger go up, while levels of hormones inducing satiety decrease. These changes persist over long periods, creating an unrelenting physiological drive to regain the lost weight.
Ghrelin
Ghrelin is produced primarily by the stomach and functions to increase hunger and promote food intake. Levels of active ghrelin increase almost immediately upon weight loss. During weight loss, ghrelin remains substantially elevated, acting to increase appetite. This persists even after weight plateaus, stimulating regain back toward the set point.
Leptin
Leptin is a hormone produced by fat cells that acts on the hypothalamus in the brain to suppress appetite. When body fat is lost after weight loss, leptin levels fall dramatically. This low leptin state is interpreted by the brain as starvation, increasing hunger and decreasing energy expenditure to promote regain of the lost fat.
Peptide YY
Peptide YY (PYY) is released from the intestines in response to eating, particularly protein and fat. By acting on appetite centers in the hypothalamus, PYY induces feelings of satiety and fullness after meals. Levels of PYY decrease rapidly with weight loss, diminishing satiety after eating. Low post-meal PYY flattens the satiety curve, promoting increased calorie intake.
Amylin
Amylin is a satiety hormone co-secreted with insulin by pancreatic beta cells during meals. Like PYY, amylin acts to induce feelings of fullness and satiety after eating. Amylin also slows gastric emptying and glucagon secretion. Weight loss significantly reduces amylin levels, decreasing satiety signals and promoting larger meal sizes.
Cholecystokinin
Cholecystokinin (CCK) is released primarily from intestinal cells in response to fat and protein consumption. Binding to receptors in the brain and vagus nerve, CCK induces satiety and decreases appetite. With weight loss, CCK levels fall, reducing satiation during meals. This decrease in meal-induced satiety contributes to increased calorie intake.
Overcoming Biology
The powerful physiological adaptations favoring weight regain present significant obstacles to long-term weight loss maintenance. However, understanding the normal biological response to weight loss creates an opportunity to work with, rather than against, the body’s innate regulatory systems.
It’s Not Your Fault
The almost irresistible urge to eat more and move less following weight loss is not due to a lack of willpower or moral failure. These drives are hardwired, involuntary biological imperatives stemming from homeostatic processes honed over eons of evolution. Blaming oneself for weight regain only adds to the challenge.
Address Root Hormonal Imbalances
The key to lasting weight loss is to address the underlying hormonal and metabolic imbalances driving increased hunger and reduced satiety, rather than trying to force caloric restriction. Potential strategies include intermittent fasting, carbohydrate restriction, stress reduction, optimized sleep, targeted exercise, and other lifestyle modifications designed to restore optimal hormone levels and metabolic function based on the individual.
Be Persistent and Patient
It takes considerable time to undo the powerful biological adaptations favoring weight regain. Progress is often slow and nonlinear. Having compassion for oneself and maintaining consistency with lifestyle changes over the
Source: Dr. Jason Fung
