The promotion of fatty acid β-oxidation by hesperidin via activating SIRT1/PGC1α to improve NAFLD induced by a high-fat diet

Reducing fat deposits in hepatocytes is a direct treatment for nonalcoholic fatty liver disease (NAFLD) and the fatty acid metabolic processes mediated by fatty acid beta-oxidation are important for the prevention of NAFLD. In this study, we established high-fat-diet models in vitro and in vivo to investigate the mechanism by which hesperidin (HDN) prevents NAFLD by modulating fatty acid beta oxidation. Based on LC-MS screening of differential metabolites, many metabolites involved in phospholipid and lipid metabolism were found to be significantly altered and closely associated with fatty acid beta-oxidation. The results from COIP experiments indicated that HDN increased the deacetylation of PGC1 alpha by SIRT1. In addition, the results of CETSA and molecular docking experiments suggest that HDN targeting of SIRT1 plays an important role in their stable binding. Meanwhile, it was found that HDN reduced fatty acid uptake and synthesis and promoted the expression of SIRT1/PGC1 alpha and fatty acid beta-oxidation, and the latter process was inhibited after transfection to knockdown SIRT1. The results suggest that HDN improves NAFLD by promoting fatty acid beta-oxidation through activating SIRT1/PGC1 alpha. Thus, the findings indicate that HDN may be a potential drug for the treatment of NAFLD.

Automated summary

This study investigated the mechanism by which hesperidin prevents nonalcoholic fatty liver disease (NAFLD) by modulating fatty acid beta oxidation. The results suggest that hesperidin promotes fatty acid beta oxidation by activating SIRT1/PGC1 alpha, thus improving NAFLD.