SIRT1 may play a crucial role in overload-induced hypertrophy of skeletal muscle

Koltai, Erika and Bori, Zoltán and Chabert, C. and Dubouchaud, H. and Naito, H. and Radák, Zsolt (2017) SIRT1 may play a crucial role in overload-induced hypertrophy of skeletal muscle. JOURNAL OF PHYSIOLOGY-LONDON, 595 (11). pp. 3361-3376. ISSN 0022-3751

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Abstract

Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well-studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus, and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in SIRT1 content and activity (P < 0.001). SIRT1-regulated Akt, eNOS, GLUT4 levels were also induced in hypertrophied muscles, and SIRT1 levels correlated with muscle mass, paired box protein 7 (Pax7), proliferating cell nuclear antigen (PCNA) and nicotinamide phosphoribosyltransferase (Nampt) levels. Alternatively, decreased FOXO1 and increased K48 polyubiquitination also suggest that SIRT1 could also be involved in the catabolic process of hypertrophy. Furthermore, increased levels of K63 and muscle RING finger 2 (MuRF2) protein could also be important enhancers of muscle mass. We report here that the levels of miR1 and miR133a decrease in hypertrophy and negatively correlate with muscle mass, SIRT1, and Nampt levels. Our results reveal a strong agreement between SIRT1 levels and activity, SIRT1 regulated pathways, and overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing. This article is protected by copyright. All rights reserved.

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