CircGLIS3 Inhibits Intramuscular Adipogenesis and Alleviates Skeletal Muscle Fat Infiltration

Area of Science:

• Molecular Biology
• Genetics
• Animal Science

Background:

• Intramuscular fat (IMF) significantly impacts meat quality and skeletal muscle function.
• Dysregulated IMF is linked to obesity and aging, with circular RNAs (circRNAs) playing a role in fat development.
• The specific functions of circRNAs in IMF deposition remain largely uncharacterized.

Purpose of the Study:

• To identify and characterize circRNAs involved in adipogenesis.
• To elucidate the role and mechanism of circGLIS3 in regulating intramuscular adipogenesis and fat infiltration.
• To explore circGLIS3 as a potential target for improving meat quality and managing metabolic disorders.

Main Methods:

• CircRNA sequencing (circRNA-seq) and weighted gene co-expression network analysis (WGCNA) for screening.
• In vitro loss-of-function and gain-of-function studies in bovine intramuscular preadipocytes and 3T3-L1 cells.
• In vivo experiments using a high-fat diet-induced mouse model.
• Mechanistic investigations including transcriptomic analysis, dual-luciferase reporter assays, RNA immunoprecipitation, and rescue experiments.

Main Results:

• A novel circRNA, circGLIS3, was identified and found to be highly expressed in bovine IMF and mouse skeletal muscle with fat infiltration.
• CircGLIS3 overexpression inhibited adipogenesis and downregulated key adipogenic genes/proteins, while knockdown promoted these processes.
• CircGLIS3 acts as a molecular sponge for miR-21-3p, upregulating its target LEPR and promoting AMPKα phosphorylation.
• Overexpression of circGLIS3 significantly reduced skeletal muscle fat infiltration in mice fed a high-fat diet.

Conclusions:

• CircGLIS3 suppresses intramuscular adipogenesis and reduces skeletal muscle fat infiltration via the miR-21-3p/LEPR/AMPK signaling pathway.
• CircGLIS3 demonstrates potential as a target for enhancing meat quality in livestock.
• CircGLIS3 may serve as a therapeutic marker for skeletal muscle fat infiltration associated with obesity.