Isoquercetin Ameliorates Obesity-Associated Muscle Atrophy and Modulates the Gut Microbiota–Bile Acid Axis

Obesity-associated muscle atrophy poses a significant health challenge. Isoquercetin (IQ) exhibits potent anti-inflammatory, antioxidant, and metabolic regulatory effects; however, whether IQ can attenuate this condition remains elusive. Thus, we employed a mouse model of HFD-induced obesity-associated muscle atrophy to assess its therapeutic potential. Compared to the HFD vehicle group, IQ treatment enhanced grip strength (>45.5%, p < 0.001), exercise capacity (>17.1%, p < 0.05), and skeletal muscle mass (>34.5%, p < 0.001). Further studies showed that IQ promoted IRβ/AKT-related insulin signaling, mTOR/S6K1-mediated protein synthesis, and AMPK/PGC1α-driven mitochondrial function pathway in skeletal muscle (all p < 0.05) and C2C12 myotubes (all p < 0.05). Additionally, IQ (400 mg/kg) treatment effectively reduced colon inflammation (2.58-fold lower of IL-1β ) and gut barrier permeability (1.66-fold lower of ZO-1 ), as well as reshaped gut microbial community and modulated bile acid composition in obese mice. Overall, these results provide novel evidence that IQ supplementation has the potential for mitigating obesity-related muscle atrophy.