Oleanolic acid attenuates obesity through modulating the lipid metabolism in high-fat diet-fed mice

As a natural pentacyclic triterpenoid, oleanolic acid has hepatoprotective, anti-inflammatory, and antioxidant activities. This work performed the in vitro experiments and animal assay to explore whether oleanolic acid alleviates lipid accumulation induced by high-fat diet by mediating PPARγ. Oil red O staining showed that oleanolic acid can reduce lipid accumulation in HepG2 cells, which were treated with oleic acid and palmitic acid. Immunofluorescence, western blot analysis, and RT-qPCR showed that oleanolic acid could promote nuclear translocation of PPARγ and reduce the expression level of PPARγ, C/EBP-β, and SREBP-1c. The results of in vivo experiments indicated that dietary intervention with oleanolic acid can effectively improve the fat accumulation in liver tissue and attenuate the level of IL-6 and TNF-α in serum caused by high-fat diet. Meanwhile, oleanolic acid did not cause lesions in vital organs at the experimental concentrations. In addition, the computer simulation indicated that oleanolic acid could directly bind to PPARγ with a reasonable and stable docking conformation. The above research results can provide new evidence for oleanolic acid to prevent nonalcoholic fatty liver disease.