A 5:2 fasting regimen curbs muscle impairment in mice

Male mice fed a high-fat diet for 14 weeks to induce metabolic dysfunction-associated steatotic liver disease underwent 12 cycles of 5:2 intermittent fasting, fasting for two days each week. Compared with continuous high-fat feeding, intermittent fasting did not significantly alter cumulative energy intake but reduced body weight, hepatic steatosis, and liver inflammation. The regimen significantly increased grip strength and skeletal muscle cross-sectional area, lowered muscle free fatty acids, and downregulated muscle inflammatory genes. In the intestine, fasting thickened the colonic wall, raised tight-junction gene expression, reduced serum lipopolysaccharide, and remodeled the gut microbiota, enriching bacteria such as Limosilactobacillus reuteri. Fasting also upregulated microbial secondary bile acid biosynthesis pathways and increased bile acid receptor expression in the gut, liver, and skeletal muscle.