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

  • J Agric Food Chem. 2026 Apr 15;74(14):11561-11578. doi: 10.1021/acs.jafc.5c16221.
Yuhua Song  1  2  3 ,  Tuo Dong  4 ,  Zhihui Fu  1  2  3 ,  Xinyue Ao  1  2  3 ,  Guang Zhao  5 ,  Yunyan Chen  1  2  3 ,  Jiayi Du  1  2  3 ,  Weiqi Wang  1  2  3 ,  Changhao Sun  1  2  3 ,  Zhen Tian  1  2  3
Affiliations
  • 1. National Key Discipline, Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin 150081, P. R. China.
  • 2. Department of Nutrition and Food Hygiene, School of Public Health, Key Laboratory of Precision Nutrition and Health, Ministry of Education, Harbin Medical University, Heilongjiang 150081, China.
  • 3. NHC Specialty Laboratory Coperation Unit of Food Safety Risk Assessment and Standard Development, Heilongjiang 150081, China.
  • 4. Department of Sanitary Microbiology, School of Public Health, Harbin Medical University, Heilongjiang 150081, China.
  • 5. Qiqihar Medical University, Heilongjiang 161006, China.
PMID: 41937383 DOI: 10.1021/acs.jafc.5c16221
Abstract

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.

Keywords
bile acid; gut microbiota; isoquercetin; mitochondrial function; obesity-associated muscle atrophy.
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