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Previous studies presented various beneficial effects of mogrosides extract from  Siraitia grosvenorii , which has been included in the list of Medicine Food Homology Species in China. Mogroside V (MV) is one of the main ingredients in mogrosides extract; however, whether and how MV improves impaired lipid metabolism in the liver remains to be elucidated. Herein, we investigated the therapeutic effects of mogroside V upon hepatic steatosis  in vivo  and  in vitro  and explored the underlying mechanisms. The results showed that MV significantly ameliorated hepatic steatosis in high-fat diet- (HFD-) fed mice. Furthermore, the increased protein expression of PPAR- γ , SREBP-1, and FASN and mRNA expression of  pparg ,  srebp1 ,  scd1 , and  fasn  in the liver in HFD-fed mice, which contribute to  de novo  lipogenesis, were dose-dependently reversed by MV treatment. Meanwhile, MV counteracted the suppressed expression of PPAR- α  and CPT-1A and mRNA expression of  atgl ,  hsl ,  ppara , and  cpt1a , thus increasing lipolysis and fatty acid oxidation. In addition, in free fatty acids- (FFAs-) incubated LO2 cells MV downregulated  de novo  lipogenesis and upregulated lipolysis and fatty acid oxidation, thereby attenuating lipid accumulation, which was significantly abrogated by treatment with Compound C, an inhibitor of AMP-activated protein kinase (AMPK). Taken together, these results suggested that MV exerted a pronounced effect upon improving hepatic steatosis through regulating the disequilibrium of lipid metabolism in the liver  via  an AMPK-dependent pathway, providing a potential lead compound candidate for preventing nonalcoholic fatty liver disease.

Mogroside V Protects against Hepatic Steatosis in Mice on a High-Fat Diet and LO2 Cells Treated with Free Fatty Acids via AMPK Activation