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Irisin, a promising but immature myokine linking between physical activity and its positive health effects

 16 April, 2018

Recently, contradictory reports were published concerning the association between the serum concentration of irisin and the physical activity level and fitness status in healthy humans. Irisin is a newly identified myokine that induces the ‘browning’ of white adipose tissue (WAT). Buscemi and colleagues studied a cohort of 858 healthy individuals in Palermo, Sicily, as a part of the ABCD (Alimentazione, Benessere Cardiovascolare e Diabete) study, and found a significant positive correlation between serum irisin concentration and habitual physical activity [1]. However, Binianinov and colleagues showed that serum irisin concentration was not related to any measures of short-term physical activity, habitual physical activity, or physical fitness in a cross-sectional analysis of 300 healthy humans who had participated in the Karlsruhe Metabolomics and Nutrition (KarMeN) study in Germany [2].


Regular physical activity and fitness are closely related to a positive healthy status in humans [2]. In this context, the muscle becomes more important due to its function as an endocrine organ. Muscle tissue secretes ‘myokines’ in response to physical activity and it is speculated that these myokines are involved in physical activity-induced positive health effects.

Irisin is a novel myokine that is secreted by muscle as a cleaved product of a membrane protein, FNDC5, whose expression is increased in response to physical activity in mice and humans [3]. Irisin induces the ‘browning’ of white adipose tissue (WAT), which is defined as the occurrence of thermogenic brown adipocytes within the WAT [4]. Rodent studies suggest that activation and/or expansion of energy-expending brown-adipose tissue (BAT) is associated with a healthy metabolic phenotype, in line with the findings in human studies that have shown an inverse association between the presence of BAT and obesity and type 2 diabetes mellitus [5]. These findings have tempted researchers to investigate the associations between the serum concentration of irisin and the physical activity level, as well as other metabolic and cardiovascular factors.

Apparently the same ELISA kits were used to measure the serum concentrations of irisin in both studies. The only remaining plausible explanation that can elucidate the discrepancy between the two studies is the participants’ residency.

According to the recent review by Polyzos and colleagues, there is some skepticism on the quality and lack of specificity of commercially available ELISA kits currently used for the measurement of circulating irisin, partly explaining the conflicts among the studies concerning the associations between irisin concentration and obesity, diabetes, and other metabolic diseases [4]. The most reliable assay proposed by the authors of the review is not widely available.

Although a quite fascinating molecule as a possible link between physical activity and its positive health effects, irisin might be too immature to be utilized in clinical practice.

Masakazu Terauchi

Department of Women’s Health, Tokyo Medical and Dental University, Tokyo, Japan


  1. Buscemi S, Corleo D, Vasto S, et al. Factors associated with circulating concentrations of irisin in the general population cohort of the ABCD study. Int J Obes (Lond) 2017;42:398-404
  2. Biniaminov N, Bandt S, Roth A, Haertel S, Neumann R, Bub A. Irisin, physical activity and fitness status in healthy humans: no association under resting conditions in a cross-sectional study. PLoS One 2018; 13:e0189254
  3. Boström P, Wu J, Jedrychowski MP, et al. A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 2012;481:463-8
  4. Polyzos SA, Anastasilakis AD, Efstathiadou ZA, et al. Irisin in metabolic diseases. Endocrine 2018;59:260-74
  5. Lidell ME, Betz MJ, Enerbäck S. Brown adipose tissue and its therapeutic potential. J Intern Med 2014;276:364-77

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