Selective androgen receptor modulation with MK-2866 favorably alters muscle mitochondrial bioenergetics

Abstract

Musculoskeletal pathologies such as sarcopenia and cachexia are increasingly prevalent within an aging global society. Musculoskeletal wasting is not limited to age and is increasingly recognized in the pathogenesis of multiple chronic diseases, including cardiometabolic disorders, such as insulin resistance and type 2 diabetes. Naturally, efforts to promote the maintenance of, if not increase in, lean mass could yield protective, disease-delaying benefits. Selective androgen receptor modulators (SARMs) have been available for several years and have recently been studied as a treatment for muscle wasting. Considering how little is known regarding the effects of SARMS on muscle mitochondrial function, and in light of the relevance of mitochondria on muscle cell dynamics, we sought to determine the specific effects of MK-2866 on muscle cell mitochondrial function. Following incubation of murine muscle cells with MK-2866, we found that mitochondrial ATP production was significantly increased, while mitochondrial respiration significantly decreased. Moreover, this same treatment regimen yielded a significant increase in muscle cell proliferation and protein synthesis. Future work will reveal the degree to which the mitochondrial changes from MK-2866 are necessary for muscle cell proliferation and protein anabolism.