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Hesperidin Protects Against High-Fat Diet-Induced Lipotoxicity in Rats by Inhibiting Pyroptosis
Ruixi Luo,Weiyi Tian,Yudie Hu,La Wang,Wenjia Wang,Ping Wang,Zunli Ke,Didong Lou 한국식품영양과학회 2024 Journal of medicinal food Vol.27 No.2
It is currently thought that excess fatty acid-induced lipotoxicity in hepatocytes is a critical initiator in thedevelopment of nonalcoholic fatty liver disease (NAFLD). Lipotoxicity can induce hepatocyte death; thus, reducing lipotoxicityis one of the most effective therapeutic methods to combat NAFLD. Abundant evidence has shown that hesperidin(HSP), a type of flavanone mainly found in citrus fruits, is able to ameliorate NAFLD, but the molecular mechanisms areunclear. We previously reported that pyroptosis contributed to NAFLD development and that inhibiting pyroptosis contributedto blunting the progression of NAFLD in rat models. Therefore, we questioned whether HSP could contribute to amelioratingNAFLD by modulating pyroptosis. In this study, a high-fat diet (HFD) induced dyslipidemia and hepatic lipotoxicity in rats,and HSP supplementation ameliorated dyslipidemia and insulin resistance. In addition, the HFD also caused pyroptosis in theliver and pancreas, while HSP supplementation ameliorated pyroptosis. In vitro, we found that HSP ameliorated palmitic acidinducedlipotoxicity and pyroptosis in HepG2 and INS-1E cells. In conclusion, we showed for the first time that HSP has aprotective effect against liver and pancreas damage in terms of pyroptosis and provides a novel mechanism for the protectiveeffects of HSP on NAFLD.
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