Reloading functionally ameliorates disuse-induced muscle atrophy by reversing mitochondrial dysfunction, and similar benefits are gained by administering a combination of mitochondrial nutrients

Abstract

We previously found that mitochondrial dysfunction occurs in disuse-induced muscle atrophy. However, the mitochondrial remodeling that occurs during reloading, an effective approach for rescuing unloading-induced atrophy, remains to be investigated. In this study, using a rat model of 3-week hindlimb unloading plus 7-day reloading, we found that reloading protected mitochondria against dysfunction, including mitochondrial loss, abnormal mitochondrial morphology, inhibited biogenesis, and activation of mitochondria-associated apoptotic signaling. Interestingly, a combination of nutrients, including α-lipoic acid, acetyl-L-carnitine, hydroxytyrosol, and CoQ10, which we designed to target mitochondria, was able to efficiently rescue muscle atrophy via a reloading-like action. It is suggested that reloading ameliorates skeletal muscle atrophy through the activation of mitochondrial biogenesis and the amelioration of oxidative stress. Nutrient administration acted similarly in unloaded rats. Here, the study of mitochondrial remodeling in rats during unloading and reloading provides a more detailed picture of the pathology of muscle atrophy.

Keywords: Acetyl-l-carnitine; CoQ(10); Free radicals; Hydroxytyrosol; Lipoic acid; Mitochondria; Muscle atrophy; Reloading; Unloading.