Irisin as a metabolic regulator of male reproduction

Abstract Obesity and metabolic syndrome are major contributors to male infertility. These conditions disrupt the hypothalamic–pituitary–gonadal (HPG) axis and compromise testicular steroidogenesis and spermatogenesis through mechanisms that include altered aromatase activity, insulin resistance, chronic inflammation, and oxidative stress. Irisin, an exercise-induced myokine, has emerged as a metabolic signal with potential effects on male reproductive function. This review summarizes irisin biology, proposed mechanisms of action, and putative functions of irisin in male reproduction, with emphasis on obesity-associated fertility impairment. Studies in high-fat diet–induced obese rodent models indicate that exogenous irisin can improve metabolic homeostasis, restore testosterone production, increase expression of key steroidogenic enzymes, and mitigate obesity-associated reductions in spermatogenesis and sperm quality. These effects are commonly attributed to anti-inflammatory, antioxidant, and cytoprotective actions, as well as modulation of cellular energy metabolism through AMP-activated protein kinase and mitogen-activated protein kinase signaling. Irisin has also been reported to influence central neuroendocrine pathways involved in gonadotropin regulation and to improve sexual behavior in rodent models of metabolic- and antidepressant-induced sexual dysfunction. However, the physiological relevance of irisin in men’s reproductive physiology remains incompletely defined. Clinical evidence is largely associative, and data on irisin receptor expression and downstream signaling in the male reproductive tract are limited. Key gaps also include the regulation of irisin secretion and potential tissue-specific actions across stages of male reproductive development. Translational studies are needed to clarify irisin’s actions within the HPG axis and gonads, and to evaluate its potential to mitigate obesity-related male reproductive dysfunction.