CircGLIS3 Inhibits Intramuscular Adipogenesis and Alleviates Skeletal Muscle Fat Infiltration

作者：Shengchen Yu, Jianfang Wang, Haibing Liu, Juntao Guo, Abebe Belete Kuraz, Yueting Pan, Anning Li, Chugang Mei, Gong Cheng, Linsen Zan · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2025 · DOI：10.1002/jcsm.70009 · 被引用次数：7 · 研究领域：Circular RNAs in diseases、Adipose Tissue and Metabolism、Chemokine receptors and signaling

BACKGROUND: Intramuscular fat (IMF) is a key determinant of meat quality. Excessive IMF deposition, commonly observed in human obesity and aging, negatively affects skeletal muscle function. Circular RNAs (circRNAs) play critical regulatory roles in muscle and fat development, as well as in the progression of related diseases. However, the specific functions and underlying mechanisms of circRNAs in IMF deposition have not been extensively studied. METHODS: We screened adipogenic differentiation-related circRNAs using circRNA-seq combined with WGCNA. Functional analyses, including loss-of-function and gain-of-function experiments, were performed to determine the role of circGLIS3 in regulating adipogenesis in bovine intramuscular preadipocytes and 3T3-L1 cells. A high-fat diet-induced mouse model was established to investigate the in vivo effects of circGLIS3 on skeletal muscle fat infiltration in mice (C57BL/6; n = 6 males). Mechanistic studies involved transcriptomic analysis, dual-luciferase reporter assays, RNA immunoprecipitation, and rescue experiments. RESULTS: We screened and characterized a novel circRNA, circGLIS3, which is highly expressed in bovine IMF tissue and in the skeletal muscle of mice exhibiting fat infiltration. Functionally, circGLIS3 overexpression inhibited triglyceride synthesis (-16.19%, p < 0.01) and lipid droplet accumulation (-42.44%, p < 0.01) in intramuscular preadipocytes, concurrently downregulating the expression of key adipogenesis-related g...