Role of Irisin in exercise training-regulated endoplasmic reticulum stress, autophagy and myogenesis in the skeletal muscle after myocardial infarction.

Abstract

Patients with heart failure (HF) are often accompanied by skeletal muscle abnormalities, which can lead to exercise intolerance and compromise daily activities. Irisin, an exercise training (ET) -induced myokine, regulates energy metabolism and skeletal muscle homeostasis. However, the precise role of Irisin in the benefits of ET on inhibiting skeletal muscle atrophy, particularly on endoplasmic reticulum (ER) stress, autophagy, and myogenesis following myocardial infarction (MI) remains unclear. In this study, we investigated the expression of Irisin protein in wild-type mice with MI, and assessed its role in the beneficial effects of ET using an Fndc5 knockout mice. Our findings revealed that MI reduced muscle fiber cross-sectional area (CSA), while downregulating the expression of Irisin, PGC-1α and SOD1. Concurrently, MI elevated the levels of ER stress and apoptosis, and inhibited autophagy in skeletal muscle. Conversely, ET mitigated ER stress and apoptosis in the skeletal muscle of infarcted mice. Notably, Fndc5 knockout worsened MI-induced ER stress and apoptosis, suppressed autophagy and myogenesis, and abrogated the beneficial effects of ET. In conclusion, our findings highlight the role of Irisin in the ET-mediated alleviation of skeletal muscle abnormalities. This study provides valuable insights into MI-induced muscle abnormalities and enhances our understanding of exercise rehabilitation mechanisms in clinical MI patients.