Shenling Baizhu San ameliorates MASLD complicated with sarcopenia-like muscle dysfunction in association with AMPKα signaling

Metabolic dysfunction-associated steatotic liver disease (MASLD) complicated with sarcopenia is associated with an increased risk of mortality and poses a substantial health burden worldwide. Shenling Baizhu San (SLBZS) shows efficacy in this comorbidity, but how it exerts this effect remains unclear. To investigate this, we established a rat model of MASLD complicated with sarcopenia-like muscle dysfunction using a HFHS diet, which shares some features of MASLD complicated with sarcopenia. Results indicated that the HFHS diet was associated with suppression of AMPKα, a key nutrient-sensing molecule within hallmarks of aging, which correlated with dysregulation of nutrient-sensing and disrupted lipid and protein homeostasis. During SLBZS treatment, the amelioration of hepatic steatosis, grip strength, muscle mass, and myosteatosis occurred in parallel with increased food intake. In the SLBZS group, elevated p-AMPKα/AMPKα and p-ACC/ACC ratios were observed in liver and skeletal muscle, consistent with enhanced AMPKα signaling. Additionally, upregulation of CPT-1 and downregulation of SREBP-1C and FAS were observed in both liver and skeletal muscle, along with decreased expression of FOXO1 and MAFbx in skeletal muscle. These findings suggest that SLBZS ameliorates HFHS-induced MASLD complicated with sarcopenia-like muscle dysfunction, and that this effect is associated with increased AMPKα signaling in both liver and skeletal muscle.