We previously reported that p-coumaric acid (PCA) ameliorated high-fat and high-sucrose (HFHS) diet-induced hepatic fibrosis in C57BL/6 mice, but the impact of PCA on HFHS-mediated muscle atrophy are not fully elucidated yet. To investigate this, we randomly divided C57BL/6 mice into three groups: low-fat diet (LF), HFHS diet (60 % kcal fat, 20 % sucrose drinking water), or HFHS + PCA (50 mg/kg BW) for 13 wk. PCA treatment (1) restored muscle fiber size by upregulating myosin heavy chain, (2) reduced lipid accumulation/lipogenesis in skeletal muscle with AMPK activation, and (3) mitigated sarcopenic features by regulating MuRF1/MAFbx, ER stress markers, and TLR/NFkB. PCA (4) improved HFHS-induced mitochondrial dysfunction, evident in enhancing oxidative phosphorylation in skeletal muscle. Palmitate (0.75 mM)-induced inhibition of myotube function and inflammation was prevented by PCA enhancing mitochondrial oxidative phosphorylation in C2C12 myotubes. These findings revealed that PCA effectively mitigates HFHS-mediated skeletal muscle atrophy by targeting muscular...

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