Myonectin protects against skeletal muscle dysfunction in male mice through activation of AMPK/PGC1α pathway

Abstract

To maintain and restore skeletal muscle mass and function is essential for healthy aging. We have found that myonectin acts as a cardioprotective myokine. Here, we investigate the effect of myonectin on skeletal muscle atrophy in various male mouse models of muscle dysfunction. Disruption of myonectin exacerbates skeletal muscle atrophy in age-associated, sciatic denervation-induced or dexamethasone (DEX)-induced muscle atrophy models. Myonectin deficiency also contributes to exacerbated mitochondrial dysfunction and reduces expression of mitochondrial biogenesis-associated genes including PGC1α in denervated muscle. Myonectin supplementation attenuates denervation-induced muscle atrophy via activation of AMPK. Myonectin also reverses DEX-induced atrophy of cultured myotubes through the AMPK/PGC1α signaling. Furthermore, myonectin treatment suppresses muscle atrophy in senescence-accelerated mouse prone (SAMP) 8 mouse model of accelerated aging or mdx mouse model of Duchenne muscular dystrophy. These data indicate that myonectin can ameliorate skeletal muscle dysfunction through AMPK/PGC1α-dependent mechanisms, suggesting that myonectin could represent a therapeutic target of muscle atrophy.

Sarcopenia and Diabetes: A Detrimental Liaison of Advancing Age

“…Preserving myokine syntheses, such as irisin, IL6, myonectin, decorin, fibroblast growth factor (FGF) 19, IL15, SPARC, and brain-derived neurotrophic factor or BDNF, results in a significant improvement in mitochondrial function and skeletal muscle metabolism, myofibrillar synthesis and skeletal muscle growth, insulin secretion, peripheral glucose and lipid utilization, with overall improvement in body composition (including fat mass loss) [ 59 , 60 , 61 ]. Moreover, suppressing the synthesis of myostatin, a potent skeletal muscle-derived transforming factor that acts as an endogenous inhibitor of myofibrillar synthesis and muscle growth, or increasing the hepatic synthesis of follistatin, a potent endogen myostatin inhibitor, can be additional strategies to improve muscle trophism.…”

Gouqi-derived nanovesicles (GqDNVs) inhibited dexamethasone-induced muscle atrophy associating with AMPK/SIRT1/PGC1α signaling pathway

“…Dexamethasone for mimicking muscle aging or muscle atrophy model has been reported in various studies [ 41 , 42 ]. In this study, we found that GqDNVs increased the grip strength and the cross-sectional area of the quadriceps muscle in the DG group after the administration of dexamethasone, which was consistent with the effect of goji [ 11 , 43 ].…”

Myokines Produced by Cultured Bovine Satellite Cells Harvested from 3- and 11-Month-Old Angus Steers

“…Additionally, there is limited to no information on these proteins in the growth and development of cattle skeletal muscle, and it would be important to evaluate whether these proteins are associated with any meat quality characteristics in the future. Other studies in biomedical model research do indicate that IL-15, CTRP15, FNDC5, and BDNF are associated with muscle growth, metabolism, and/or repair [ 49 , 50 , 51 , 52 , 53 , 54 ], and it is possible that future studies of these myokines in cattle may identify similar effects on muscle in vivo. IL-6 has been shown to cause muscle atrophy with long-term high exposure but does have properties that still support muscle growth in humans and mice [ 55 , 56 , 57 ].…”