Phytosterols ameliorate high-fat diet-induced sarcopenic obesity and skeletal muscle mitochondrial dynamics dysfunction via intestinal microbiota reshaping

• Phytosterols (PS) effectively ameliorates high-fat diet-induced sarcopenic obesity through gut microbiota remodeling. • PS enriches beneficial bacteria and mediates gut microbiota-muscle axis anti-inflammatory mechanisms • PS regulates mitochondrial dynamics and muscle atrophy transcriptional networks • Fecal microbiota transplantation confirms PS protective effects through gut microbiota Sarcopenic obesity (SO) is prevalent and linked to intramuscular fat accumulation under hyperlipidemia. Phytosterols (PS) can reduce hyperlipidemia by inhibiting intestinal cholesterol absorption and modulating gut microbiota. In this study, we employed a high-fat diet (HFD) rat model to investigate the therapeutic potential of dietary PS supplementation against SO. HFD-induced SO rats received oral PS for 12 weeks. We assessed body weight, grip strength, serum inflammatory markers, and intestinal barrier indicators. Gut microbiota was profiled by 16S rRNA sequencing, and skeletal muscle proteins were analyzed by Western blot. Fecal microbiota transplantation (FMT) tested microbiota causality. PS treatment resulted in a 1.48-fold increase in relative grip strength and a 1.18-fold increase in the median muscle fiber cross-sectional area compared with the HFD group. PS treatment significantly attenuated systemic chronic inflammation, reducing circulating pro-inflammatory cytokines-TNF-α by 33.21%, IL-1β by 43.66%, and IL-6 by 43.54%-compared with the HFD group (all P