MG5012 andsubsp.MG741 Alleviate Metabolic Dysfunction-Associated Steatotic Liver Disease and Preserve Skeletal Muscle Integrity in High-Fat-Diet-Fed Mice.

Abstract

BACKGROUND/OBJECTIVES: This study investigated the systemic metabolic effects of two probiotic strains,MG5012 andsubsp.MG741, on metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity-related muscle dysfunction in high-fat-diet (HFD)-induced obese mice. METHODS: Obesity was induced in C57BL/6 mice via high-fat diet (HFD) feeding for 6 weeks. Subsequently, the mice were orally administered MG5012 or MG741 for 8 weeks. We assessed systemic metabolic parameters, including body weight, adiposity, and serum biomarkers. Additionally, histological and molecular analyses were performed to evaluate hepatic steatosis, intestinal barrier integrity, and muscle oxidative status. RESULTS: Both strains significantly attenuated body weight gain and adiposity, reduced serum liver injury markers (γ-GTP, ALT, AST), and improved systemic metabolic parameters by restoring serum GLP-1 levels and reducing hyperinsulinemia. Crucially, MG5012 and MG741 strengthened intestinal barrier integrity by upregulating the tight junction proteins Occludin and Claudin-1. In the liver, histological analyses revealed reductions in hepatic steatosis and triglyceride content, accompanied by the downregulation of lipogenic genes (SREBP-1c, FAS). Furthermore, the probiotics preserved skeletal muscle integrity; while muscle weight remained unchanged, the strains increased muscle fiber cross-sectional area (CSA) and reduced serum markers of muscle damage (CPK, LDH). This protective effect was associated with significantly enhanced expression of antioxidant enzymes (SOD, CAT, GPx) in muscle tissue. CONCLUSIONS: These findings suggest that MG5012 and MG741 confer systemic metabolic benefits through the modulation of the gut-liver-muscle axis and may serve as promising functional food ingredients for the management of MASLD and obesity-associated muscle atrophy.