Satellite cell content and muscle regeneration in a mouse model of NAFLD

Objectives: Muscle wasting is a common complication in patients with nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the effect of NAFLD on satellite cell (SC) content and skeletal muscle repair.

Methods: Male CD-1 mice fed a choline-deficient diet for 4 wk were used as an NAFLD model. We performed histologic and mRNA expression analyses, immunochemical staining with single muscle fibers to assess the effect of NAFLD on muscle Pax7+ SCs, and muscle regeneration by intramuscular injection of cardiotoxin.

Results: We found that the total number of Pax7+ SCs in the extensor digitorum longus and tibialis anterior muscles of mice with NAFLD was significantly decreased when compared with that in the control group, in which the depletion of the SC pool possibly impaired muscle regeneration, as evidenced by the smaller size of the regenerating myofibers. Importantly, we found that NAFLD significantly impaired the differentiation ability of SCs, as shown by a decreased number of SCs expressing a myogenic marker, MyoD. Finally, this study indicated that molecular mechanisms underlying a decline in SC numbers may be attributed to the upregulation of proinflammatory cytokines (tumor necrosis factor α [TNFα]) and an oxidative stress marker (NADPH oxidase-2 [NOX2\) in mice with NAFLD.

Conclusions: The findings demonstrate that a decrease in SC content in the skeletal muscle is an important factor that contributes to muscle wasting in NAFLD. Thus, preservation of the muscle SC pool is a potential therapeutic strategy to reduce NAFLD-associated muscle wasting.