1. RORα–GABP–TFAM axis alleviates myosteatosis with fatty atrophy through reinforcement of mitochondrial capacity
- Author
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Hyeon‐Ji Kim, Sang‐Heon Lee, Cheolhee Jeong, Yong‐Hyun Han, and Mi‐Ock Lee
- Subjects
fatty atrophy ,mitochondrial biogenesis ,myosteatosis ,NAFLD ,RORα ,Diseases of the musculoskeletal system ,RC925-935 ,Human anatomy ,QM1-695 - Abstract
Abstract Background Fat infiltration in muscle, called ‘myosteatosis’, precedes muscle atrophy, which subsequently results in sarcopenia. Myosteatosis is frequently observed in patients with nonalcoholic fatty liver disease (NAFLD). We have previously reported that retinoic acid receptor‐related orphan receptor‐α (RORα) regulates mitochondrial dynamics and mitophagy in hepatocytes, resulting in an alleviation of NAFLD. In this study, we aimed to investigate the role of RORα in skeletal muscle and to understand molecular mechanisms by which RORα controls mitochondrial capacity, using an NAFLD‐associated myosteatosis mouse model. Methods To establish a myosteatosis model, 7‐week‐old C57BL/6N mice were fed with high‐fat diet (HFD). After 15 weeks of diet feeding, an adeno‐associated virus vector encoding RORα (AAV‐RORα) was injected to gastrocnemius (GA) muscles, or after 7 weeks of HFD feeding, JC1‐40, an RORα agonistic ligand, was administered daily at a dose of 5 mg/kg/day by oral gavage for 5 weeks. Histological, biochemical and molecular analyses in various in vivo and in vitro experiments were performed. Results First, the number of oxidative MyHC2a fibres with intensive lipid infiltration increased by 3.8‐fold in the red region of the GA of mice with myosteatosis (P
- Published
- 2024
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