on June 29, 2026
Weight loss is often described as a simple mathematical subtraction of calories consumed from calories taken in. Although energy balance remains a fundamental biological law, modern physiology shows that the human body does not manage weight like a simple calorie counter.
The regulation of body composition depends on a network of endocrine and nervous signals involving adipose tissue, the gut, the pancreas, muscle, and the brain.
Among the molecules that have received increasing attention in metabolic research are adiponectin, leptin, resistin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide YY (PYY).
These molecules do not, on their own, determine weight loss or gain, but they participate in a dynamic system that influences hunger, satiety, energy expenditure, and nutrient allocation.
Adipose tissue as an endocrine organ
For many years, body fat was considered a simple energy store.
We now know that adipose tissue is an active endocrine organ capable of producing numerous signaling molecules called adipokines.
These include:
leptin,
adiponectin,
resistin,
visfatin,
proinflammatory cytokines.
These substances enable the brain to receive information about the state of energy stores.
Adiponectin: a signal of metabolic flexibility
Adiponectin is a protein secreted mainly by adipocytes.
Contrary to what its name might suggest, it does not directly “melt” fat but plays a role in regulating lipid and carbohydrate metabolism.
One of the most interesting findings is that plasma adiponectin concentrations tend to decrease in visceral obesity and rise when metabolic function improves.
The main documented effects include:
improved insulin sensitivity,
increased fatty acid oxidation,
reduced levels of certain inflammatory signals,
activation of AMPK-related metabolic pathways.
During weight-loss programs associated with improved metabolic health, adiponectin levels may increase.
This phenomenon is not interpreted as a simple effect of weight loss, but as a sign of improved adipose tissue function.
Adiponectin, leptin, and the brain: communication with the hypothalamus
The hypothalamus is one of the main centers for energy integration.
It continuously receives information about:
energy availability,
the filling of energy stores,
nutritional status,
hunger and satiety.
Leptin primarily communicates the level of adipose stores.
When the brain detects a marked reduction in energy availability, it may increase hunger and reduce energy expenditure through metabolic adaptations.
Adiponectin, by contrast, appears to act as a modulator of metabolic sensitivity and the availability of energy substrates for use.
Physiological weight loss therefore does not depend on a single molecule, but on the coordination of signals that enable fat to be used without excessively activating defensive energy-conservation mechanisms.
Inflammation, resistin, and the metabolism of fat storage
Chronic low-grade inflammation is a key factor in the regulation of body weight.
Resistin belongs to the group of adipokines involved in immune-metabolic communication.
In humans, much of the resistin comes from immune cells rather than exclusively from adipocytes.
High levels have been associated in numerous observational studies with:
reduced insulin sensitivity,
increased inflammatory markers,
metabolic alterations.
Chronic inflammation contributes to less efficient insulin signaling.
This does not mean that resistin alone causes weight gain, but that persistent inflammatory conditions can contribute to creating a biological environment that is less favorable to the efficient use of energy.
CCK: satiety that begins in the stomach and intestine
Cholecystokinin (CCK) is one of the main satiety hormones.
It is secreted by intestinal cells, especially in response to the presence of fats and proteins.
Its functions include:
slowed gastric emptying,
digestive stimulation,
activation of nerve signals to the brain.
Through the vagus nerve and hypothalamic circuits, it contributes to the cessation of the meal.
The satiating effect depends not only on the lipid content but also on the volume and structure of the meal.
For this reason, foods naturally rich in fiber and unsaturated fats can generate greater satiety compared to highly processed products.
Oilseeds, legumes, whole grains, and balanced meals are examples of food matrices that promote a more gradual response.
Why ultra-processed foods often do not satisfy
Highly processed foods tend to have:
high energy density,
low fiber content,
and rapid digestive availability.
This promotes less stimulation of the mechanical and hormonal mechanisms of satiety.
It is not correct to say that all “light” products increase hunger, but foods low in fiber and not very satiating can make it more difficult to spontaneously control energy intake.
GLP-1: the intestinal sensor of energy abundance
GLP-1 is a hormone produced by L cells in the intestine.
Its secretion increases after a meal, especially in response to the presence of nutrients.
Its actions include:
slowed gastric emptying,
increased satiety,
and enhanced glucose-dependent insulin secretion.
GLP-1 is not activated exclusively when sugar levels are excessive.
Instead, it is one of the main physiological systems that help the body coordinate digestion and metabolism after eating.
In type 2 diabetes, the so-called incretin effect may be reduced.
To physiologically support these mechanisms, the following are useful:
moderation of simple sugars,
presence of protein,
presence of quality fats,
fiber-rich foods.
PYY: the signal that invites you to finish your meal
Peptide YY is secreted mainly in the final portion of the intestine.
Its secretion increases especially after meals containing protein and fat.
Its actions include:
appetite reduction,
slowed digestive motility,
integration with GLP-1 and CCK.
Nutritional studies suggest that dietary patterns rich in viscous fibers and whole grains can promote a more favorable response of the satiety system.
Time spent eating and chewing also seem to influence the gut-brain dialogue.
Losing weight does not mean eating less: it means generating consistent metabolic signals
Body weight maintenance depends not only on the quantity of food but also on the quality of the biological signal generated.
Regular physical activity, adequate protein intake, dietary fiber, complete meals, and sustainable eating habits work together on the systems that regulate hunger and energy consumption.
The goal is not to force metabolism but to create conditions in which the body can use energy efficiently without activating chronic defense mechanisms.
Bibliography
Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors.
Ahima RS. Adipose tissue as an endocrine organ.
Friedman JM. Leptin and regulation of body weight.
Steppan CM et al. The hormone resistin links obesity to diabetes.
Rowland NE et al. Cholecystokinin effects on feeding.
Holst JJ. The physiology of GLP-1.
Drucker DJ. Mechanisms of action of GLP-1.
Batterham RL et al. Gut hormone PYY and appetite regulation.
Slavin JL. Dietary fiber and satiety.
Hall KD et al. Ultra-processed diets cause excess calorie intake.
Morton GJ et al. Central nervous system control of food intake.
