Digital illustration of irisin connecting muscles, fat cells, heart, pancreas, and brain.

Irisin: The Exercise Hormone's Role in Metabolic Health

Reese Marlowe in Health & Wellness December 2025 • 4 min read.

"Exploring the science behind irisin, a myokine linked to exercise and its potential impact on obesity, diabetes, and cardiovascular health."

In an era where the benefits of exercise are constantly touted, scientists have been diligently working to unravel the specific mechanisms that make physical activity so beneficial. Among the key discoveries is irisin, a myokine/adipokine released primarily by muscles during exercise. This hormone has garnered significant attention for its potential role in "browning" white adipose tissue, enhancing thermogenesis, and boosting energy expenditure.

Since its identification, irisin has been linked to a range of favorable effects on metabolic diseases. Conditions such as obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and metabolic bone diseases have all been associated with irisin activity. While promising results have been observed in rodents, the effects of irisin in humans are still being explored to a great extend.

This article aims to provide an in-depth review of the current understanding of irisin, its mechanisms, and its implications for various metabolic disorders. We'll explore the latest research, discuss the challenges in studying this hormone, and consider its potential as a therapeutic target for improving metabolic health.

Irisin and Obesity: What's the Connection?

Digital illustration of irisin connecting muscles, fat cells, heart, pancreas, and brain.

The relationship between irisin and obesity is a central focus in metabolic research. White adipose tissue (WAT), the primary site for energy storage, is now considered a significant endocrine organ. Irisin's ability to induce "browning" in WAT—transforming it into more metabolically active, brown-like fat—has sparked interest in its potential to combat obesity.

In this context, studies reveal nuanced and sometimes conflicting results, emphasizing the complexity of irisin's actions:

Rodent Studies: In rodents, FNDC5/irisin is secreted mainly from subcutaneous adipose tissue (SAT), with lower amounts from visceral adipose tissue (VAT). WAT-derived irisin can constitute up to 30% of circulating levels and is further elevated after exercise. In obese mice, injecting FNDC5-expressing adenoviral particles or recombinant human irisin improves glucose metabolism, but has minor effects on body weight.
Human Studies: In humans, FNDC5 expression is 100–200 times lower in WAT than in muscle, indicating that WAT’s contribution to circulating irisin levels is minor. Once released into circulation, irisin stimulates UCP1 expression and WAT browning, increasing total body energy expenditure.
In Vitro vs. In Vivo: In human preadipocytes from SAT, irisin inhibits differentiation into mature adipocytes, decreasing browning-related genes. Conversely, in mature human adipocytes, irisin stimulates browning, as indicated by increased UCP1 and PRDM16 expression, probably through the activation of the p38 MAPK and ERK signaling pathways.

Human research exploring the correlations between circulating irisin levels and obesity presents a mixed picture. While most studies report a positive association between irisin and body mass index (BMI) and weight, it is not universally consistent. Patients with anorexia nervosa show lower circulating irisin levels compared to normal-weight individuals, while morbidly obese individuals have even higher levels. Irisin also correlates positively with fat mass, waist circumference, and muscle mass.

The Future of Irisin Research

Irisin holds considerable promise as a therapeutic target for metabolic diseases. It emphasizes the intricate relationship between exercise, muscle function, and overall metabolic health. Further research is necessary to fully understand the physiological roles of irisin and to harness its therapeutic potential.

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This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1007/s12020-017-1476-1, Alternate LINK

Title: Irisin In Metabolic Diseases

Subject: Endocrinology

Journal: Endocrine

Publisher: Springer Science and Business Media LLC

Authors: Stergios A. Polyzos, Athanasios D. Anastasilakis, Zoe A. Efstathiadou, Polyzois Makras, Nikolaos Perakakis, Jannis Kountouras, Christos S. Mantzoros

Published: 2017-11-23

Everything You Need To Know

What is Irisin?

Irisin is a myokine/adipokine, a hormone primarily released by muscles during exercise. Its discovery has been significant because it has been linked to several beneficial effects on metabolic diseases, including obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and metabolic bone diseases. These conditions impact a large population, and understanding irisin's role is crucial for potential therapeutic interventions.

What is the main function of Irisin?

The primary function of Irisin is to induce "browning" in white adipose tissue (WAT). WAT is a major site for energy storage and is now recognized as an endocrine organ. By converting WAT to brown-like fat, Irisin enhances thermogenesis (heat production) and boosts energy expenditure, which is potentially beneficial for combating obesity. This process involves the stimulation of UCP1 expression and activation of signaling pathways like p38 MAPK and ERK. The process of browning is more complex than it initially seems.

What are the implications of Irisin research?

Research indicates complex implications depending on the organism and specific type of adipose tissue. In rodents, the secretion of FNDC5/irisin occurs mainly from subcutaneous adipose tissue (SAT). In human preadipocytes from SAT, Irisin inhibits differentiation into mature adipocytes. In mature human adipocytes, Irisin stimulates browning. Human studies show mixed results on the correlation between Irisin levels, BMI, and weight. More studies are needed to determine the therapeutic role of Irisin.

What are the challenges in studying Irisin?

Current research faces the challenge of reconciling the inconsistent findings observed in both rodent and human studies. The variation in results could be due to several factors, including differences in experimental design, the specific populations studied, and the varying levels of physical activity among participants. Further research is needed to fully understand the physiological roles of Irisin and how to harness its potential therapeutic effects. These challenges highlight the importance of continuing research to refine our understanding of Irisin's effects.

Why is Irisin considered a potential therapeutic target?

Irisin holds promise as a therapeutic target because of its potential to impact metabolic diseases. Because of its role in enhancing energy expenditure and improving metabolic health, it could lead to novel treatments for obesity, type 2 diabetes, and other related conditions. Future research will likely focus on identifying ways to safely and effectively increase Irisin levels or mimic its effects, offering new strategies for preventing and managing metabolic disorders, especially since exercise is not always accessible or feasible for everyone. The findings have shown promising results, but additional research is needed.