Irisin, Energy Homeostasis and Male Reproduction

Abstract

Irisin is a novel skeletal muscle- and adipose tissue-secreted peptide. It is conventionally regarded as an adipomyokine and is a cleaved fragment of Fibronectin type III domain-containing protein 5 (FNDC5). It is involved in the browning of white adipose tissue, glucose tolerance, and reversing of metabolic disruptions. Fertility is closely linked to energy metabolism and the endocrine function of the adipose tissue. Moreover, there is established association between obesity and male infertility. Irisin bears strong therapeutic promise in obesity and its associated disorders, as well as shown to improve male reproductive functions. Thus, irisin is a molecule of great interest in exploring the amelioration of metabolic syndrome or obesity-induced male infertility. In this review we aim to enumerate the most significant aspects of irisin actions and discuss its involvement in energy homeostasis and male reproduction. Though current and future research on irisin is very promiscuous, a number of clarifications are still needed to reveal its full potential as a significant medicinal target in several human diseases including male infertility.

Keywords: energy metabolism; irisin; male infertility; metabolic syndrome; reproduction.

FIGURE 1

Expression and detection of Fibronectin type III domain containing 5 (FNDC5). (A) Global expression and detection of FNDC5 RNA/protein; (B) FNDC5 RNA (normalized expression) and protein expression in overall male reproductive tissues and specific testicular cells.

FIGURE 2

Mechanism of irisin actions linking energy homeostasis, obesity, inflammation, and male reproduction. (A) Irisin acts via activation of the AMP activated protein kinase (AMPK), P38, MAPK (mitogen activated protein kinase) pathway; (B) irisin-activated pathway upregulates glucose transporter 4 (GLUT4) expression and transportation to membrane, aiding cellular glucose uptake that follows increased glucose metabolism and energy expenditure; (C) irisin also induces the expression of mitochondrial uncoupling protein 1 (UCP1) that aids conversion of white adipose tissue to brown adipose tissue, resulting in raised total body energy expenditure, as well as facilitates pancreatic β-cell regeneration that contribute to irisin-mediated reversing of insulin resistance; (D) irisin downregulates nuclear factor kappa-B (NF-kB) thereby playing role in suppressing inflammatory responses; (E) irisin-induced activation of Nrf2 (nuclear factor erythroid-2 related factor) may increase production of antioxidant enzymes thereby curbing excess reactive oxygen species (ROS) and oxidative stress (OS); (F) irisin may act on the HPG (hypothalamic-pituitary-gonadal) axis or directly upon the testicular cells to regulate male reproductive functions. Moreover, irisin actions to improve metabolic balance as well as to reverse obesity, inflammation and OS, may confer ameliorative impact upon obesity/inflammation/OS-mediated male infertility.