Irisin prevents dexamethasone-induced atrophy in C2C12 myotubes

In Deok Kong,Jae Seung Chang

doi:10.1007/s00424-020-02367-4

In Deok Kong, Jae Seung Chang

Open Access

https://doi.org/10.1007/s00424-020-02367-4

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Abstract

Irisin is a myokine secreted mainly from skeletal muscle that is known for having beneficial metabolic effects via enhancement of energy expenditure and insulin sensitivity. Studies show that irisin also acts as an autocrine/paracrine to promote myogenesis and muscle growth. However, the protective role of irisin against muscular wasting remains unclear. We confirmed that irisin secretion was upregulated by electrical pulse stimulation an in vitro exercise mimetic model. Next, we tested if irisin exerted an anti-atrophic effect on cultured C2C12 myotubes treated with dexamethasone (DEX), a representative inducer of muscular atrophy. Treatment of cultured myotubes with DEX reduced myotube size and increased proteasome activity, which were attenuated by irisin. Also, irisin effectively prevented dephosphorylation of forkhead box O (FoxO) 3α and upregulation of muscle-specific ubiquitin ligases in DEX-treated myotubes. The protective effect of irisin on DEX-mediated myotube atrophy was partially regulated by insulin-like growth factor-1-dependent signaling. These results suggested that irisin may prevent glucocorticoid-induced muscle atrophy by inhibiting FoxO-mediated ubiquitin-proteasome overactivity.

Highlights

Skeletal muscle atrophy is a debilitating consequence of physiological processes and conditions such as disuse, malnutrition, and aging
Circulating irisin is upregulated by both endurance and strength exercise, and its levels positively correlate with indicators of skeletal muscle mass and levels of insulin-like growth factor-1 (IGF-1), an anabolic hormone of skeletal muscle [10, 13, 18]
Reports indicate that irisin positively affects myogenesis by enhancing intramuscular anabolic signaling and protects against unloading- or denervation-induced muscle wasting [7, 26]

Summary

Introduction

Skeletal muscle atrophy is a debilitating consequence of physiological processes and conditions such as disuse, malnutrition, and aging. It is a prominent pathological feature of chronic illnesses including cardiac or renal failure, chronic obstructive pulmonary disease, liver cirrhosis, and cancer [6, 11]. Circulating irisin is upregulated by both endurance and strength exercise, and its levels positively correlate with indicators of skeletal muscle mass and levels of insulin-like growth factor-1 (IGF-1), an anabolic hormone of skeletal muscle [10, 13, 18]. Mice with null mutations in myostatin, a main negative regulator of muscle growth, display elevated irisin levels and increased muscle growth-related gene

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