on June 30, 2026
The human body regulates body weight through an extremely sophisticated network of metabolic, endocrine, immune, and nutritional signals. Fat mass is not simply an energy reserve, just as muscle is not merely a structure dedicated to movement. Today we know that muscle tissue is a true endocrine organ capable of producing signaling molecules called myokines, which can influence energy metabolism, insulin sensitivity, systemic inflammation, and exercise adaptation.
Among these molecules, one of the most studied in recent years is irisin, a myokine identified in 2012 and derived from the proteolysis of the FNDC5 membrane protein (fibronectin type III domain-containing protein 5). Its production increases in response to muscle contraction and appears closely linked to the activation of the transcriptional coactivator PGC-1α, one of the main regulators of mitochondrial biogenesis and metabolic adaptation to exercise.
Scientific interest in irisin stems from the hypothesis that muscle can communicate with adipose tissue and other organs by inducing metabolic changes favorable to body weight control and metabolic health.
One of the most discussed mechanisms concerns irisin's ability to promote the so-called “browning” of white adipose tissue. White adipose tissue primarily serves as an energy storage depot, while brown adipose tissue is specialized in dissipating energy in the form of heat through the process of thermogenesis.
Numerous experimental studies have shown that irisin can induce the expression of genes typical of brown or beige adipocytes in white adipose depots, increasing the expression of the UCP1 protein (Uncoupling Protein 1). This protein acts at the mitochondrial level by uncoupling ATP production from the respiratory chain: part of the energy that would normally be converted into chemical energy is dissipated in the form of heat.
It is important to clarify that in humans, irisin's quantitative contribution to weight loss does not yet appear to be defined with the same strength observed in animal models. However, the biological concept remains extremely relevant: active muscle produces signals that tend to orient metabolism toward greater energy utilization.
Physical exercise not only determines an increase in calorie consumption during exertion, but also induces a profound metabolic reprogramming that continues in the hours and days that follow. The increase in mitochondrial oxidative capacity, the improvement of insulin function, and greater metabolic flexibility probably constitute more important effects than simple acute energy expenditure.
Moderate-intensity, prolonged physical activity promotes cardiovascular adaptations and an increase in the ability to use fatty acids as an energy substrate. At the same time, more intense sessions—depending on age, clinical conditions, and training level—can stimulate a greater release of myokines, the recruitment of fast-twitch muscle fibers, and the post-exercise metabolic response.
High-intensity interval training (HIIT), pace variations, uphill work, and strength sessions show in several studies greater effectiveness in preserving lean mass and improving certain metabolic markers compared to continuous low-intensity exercise alone.
This does not mean that weight loss depends exclusively on training intensity. The reduction of fat mass remains the result of the interaction between energy balance, nutritional quality, body composition, hormonal status, sleep, and behavioral consistency.
Irisin also appears to exert favorable effects on insulin sensitivity. Insulin resistance represents one of the main mechanisms underlying visceral fat accumulation, metabolic syndrome, and altered glycemic regulation.
Several studies have suggested that muscle activity promotes glucose transport into cells through mechanisms partly independent of insulin, involving GLUT4 transporters, AMPK activation, and mitochondrial modifications. Irisin could fit into this network of signals, contributing to the improvement of the insulin response.
Alongside physical activity, the concept of daily biological load takes on a central role. The body has extraordinarily efficient defense systems against occasional exposure to potentially harmful substances: free radicals, products of intense cooking, food contaminants, or transient oxidative stress are generally neutralized through endogenous antioxidant systems.
The problem arises when the overload becomes chronic. Hypercaloric diet, excess ultra-processed foods, sedentary lifestyle, sleep deprivation, and persistent stress determine a state of low-grade chronic inflammation that progressively alters metabolic regulation systems.
This state, defined as meta-inflammation, is today considered one of the main factors involved in the development of obesity, type 2 diabetes, fatty liver, sarcopenia, and cardiovascular diseases.
Another element that is receiving increasing attention is nutritional chronobiology.
The human body does not metabolize calories in the same way throughout the day. Circadian rhythms coordinate hormone secretion, insulin sensitivity, mitochondrial activity, and appetite regulation.
In the morning hours, there is physiologically observed increase in cortisol and greater metabolic efficiency in glucose management. Insulin sensitivity tends to decrease in the evening hours.
Several clinical studies suggest that concentrating a greater portion of calorie intake in the early hours of the day may be associated with better glycemic control, greater satiety, and better weight management compared to a diet heavily shifted toward the evening.
These data do not authorize simplifications such as “you always gain weight in the evening,” but indicate that nutritional timing can contribute to overall metabolic efficiency.
The quality of the protein intake also represents a key element of metabolism.
Proteins provide essential amino acids for the synthesis of muscle, collagen, bone matrix, enzymes, receptors, peptide hormones, plasma transporters, and immune molecules.
Insufficient amino acid availability can reduce muscle protein synthesis and compromise recovery processes, exercise adaptation, and maintenance of lean mass.
Plant proteins can effectively support anabolism when included in a well-planned and sufficiently varied diet. Legumes, seeds, nuts, soy derivatives, whole grains, and appropriate food combinations generally allow for an adequate amino acid profile.
The traditional concept of “biological value” has today been partly superseded by more modern indicators such as PDCAAS and DIAAS, which consider digestibility and the actual availability of amino acids.
The idea that plant proteins necessarily generate a greater nitrogenous waste load compared to animal proteins is not generally confirmed in contemporary literature. Overall protein quality depends on the global dietary pattern.
According to international reference data, the protein requirement for a healthy adult is approximately 0.8–0.83 g/kg/day.
This requirement increases in numerous physiological or clinical conditions: growth, pregnancy, breastfeeding, post-illness recovery, intense sports activity, calorie restriction, aging, and sarcopenia prevention.
For active individuals or the elderly, numerous scientific societies suggest intakes between 1.0 and 1.6 g/kg/day, with higher values in specific sports conditions.
From a practical standpoint, a diet model oriented toward metabolic health should favor minimally processed foods, an adequate protein intake, high micronutrient density, balanced meal distribution, and integration with exercise programs that combine aerobic resistance and muscle stimulation.
Stable weight loss therefore does not appear to be the result of a single molecule, an extreme strategy, or aggressive calorie restriction, but rather the expression of a complex biological regulation in which muscle, circadian rhythm, and nutritional quality collaborate to determine favorable long-term adaptations.
Bibliography
Boström P et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012.
Huh JY et al. Irisin in response to exercise in humans. Diabetologia. 2014.
Fox J et al. The clinical relevance of irisin. Front Endocrinol. 2018.
Pedersen BK, Febbraio MA. Muscles, exercise and obesity. Cell Metabolism. 2012.
Hawley JA et al. Integrative biology of exercise. Cell. 2014.
Boutcher SH. High-intensity intermittent exercise and fat loss. J Obes. 2011.
Sutton EF et al. Early Time-Restricted Feeding Improves Insulin Sensitivity. Cell Metabolism. 2018.
Jakubowicz D et al. High caloric intake at breakfast vs dinner differentially influences weight loss. Obesity. 2013.
EFSA Panel on Dietetic Products, Nutrition and Allergies. Dietary reference values for protein. EFSA Journal. 2012.
WHO/FAO/UNU. Protein and Amino Acid Requirements in Human Nutrition. WHO Technical Report Series.
Phillips SM, Van Loon LJC. Dietary protein for athletes. J Sports Sci. 2011.
Bauer J et al. Evidence-based recommendations for optimal dietary protein intake in older people. JAMDA. 2013.
