Irisin alleviates obesity-related spermatogenesis dysfunction via the regulation of the AMPK\u03b1 signalling pathway

Ling-Bo Luo,Jing Yang,Yang Mu,Huang-Guan Dai

doi:10.1186/s12958-021-00821-1

Abstract

BackgroundInfertility is a common complication in obese men. Oxidative stress and testicular apoptosis play critical roles in obesity-induced spermatogenesis dysfunction. It has been reported that irisin, an exercise-induced myokine, may attenuate oxidative damage and testicular apoptosis in several diseases; however, its role in obesity-induced spermatogenesis dysfunction remains unclear. The purpose of this study was to investigate the role and underlying mechanism of irisin in obesity-induced dysfunction of spermatogenesis.MethodsMale mice were fed a high-fat diet (HFD) for 24 weeks to establish a model of obesity-induced spermatogenesis dysfunction. To explore the effects of irisin, mice were subcutaneously infused with recombinant irisin for 8 weeks beginning at 16 weeks after starting a HFD. To confirm the role of AMP-activated protein kinase α (AMPKα), AMPKα-deficient mice were used.ResultsThe data showed decreased serum irisin levels in obese patients, which was negatively correlated with sperm count and progressive motility. Irisin was downregulated in the plasma and testes of obese mice. Supplementation with irisin protected against HFD-induced spermatogenesis dysfunction and increased testosterone levels in mice. HFD-induced oxidative stress, endoplasmic reticulum (ER) stress and testicular apoptosis were largely attenuated by irisin treatment. Mechanistically, we identified that irisin activated the AMPKα signalling pathway. With AMPKα depletion, we found that the protective effects of irisin on spermatogenesis dysfunction were abolished in vivo and in vitro.ConclusionsIn conclusion, we found that irisin alleviated obesity-related spermatogenesis dysfunction via activation of the AMPKα signalling pathway. Based on these findings, we hypothesized that irisin is a potential therapeutic agent against obesity-related spermatogenesis dysfunction.

Highlights

Infertility is a disease defined as the failure to establish a successful clinical pregnancy after at least 1 year of regular and unprotected sexual intercourse; presently, Mu et al Reprod Biol Endocrinol (2021) 19:135Previous studies have demonstrated that reactive oxygen species (ROS)-mediated damage to spermatozoa is a major cause of male infertility and affects nearly 30%80% of infertile men [5, 6]
Irisin was downregulated in obese patients and mice To elucidate the role of irisin in obesity-induced male infertility, we first measured irisin levels in obese patients
Correlation analysis revealed that plasma irisin levels were negatively correlated with sperm count and progressive motility (Fig. 1B-C)

Summary

Introduction

Previous studies have demonstrated that reactive oxygen species (ROS)-mediated damage to spermatozoa is a major cause of male infertility and affects nearly 30%80% of infertile men [5, 6]. Oxidative stress has adverse effects on both the functional and structural integrity of spermatozoa, which leads to sperm cell dysfunction and male infertility [7,8,9,10]. Our previous study reported that ER stress played a key role in obesityinduced reproductive dysfunction [20, 21]. Oxidative stress and testicular apoptosis play critical roles in obesity-induced spermatogenesis dysfunction. It has been reported that irisin, an exercise-induced myokine, may attenuate oxidative damage and testicular apoptosis in several diseases; its role in obesityinduced spermatogenesis dysfunction remains unclear. The purpose of this study was to investigate the role and underlying mechanism of irisin in obesity-induced dysfunction of spermatogenesis

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Conclusion