Asiatic acid promotes liver fatty acid metabolism in diabetic models

Asiatic acid (AA) has lipid-lowering and anti-diabetic properties. This study aimed to investigate the effects of AA on liver fatty acid metabolism. A mouse model of spontaneous type 2 diabetes was established by administering a high-fat diet to db/db mice. After treatment with AA for four weeks, liver morphology, fat synthesis, oxidation-related gene expression, and adenosine 5'-monophosphate- activated protein kinase (AMPK) signaling were assessed. The capacity of AA to protect against dysfunctional metabolism was also assessed in a free fatty acid (FFA)-induced hepatic cell line. Model mice weighed more and had heavier livers, higher ratios of liver to body weight, and higher levels of fasting serum glucose, cholesterol, and triglycerides, than control mice. AA treatment ameliorated these changes. Importantly, AA treatment reversed abnormal expression of SREBP1c, FAS, ACC1, SIRT1, PGC1 alpha, PPAR alpha, and CPT1 alpha. In vitro, it was observed that AA reduced expression of genes associated with fatty acid synthesis and increased expression of genes associated with fatty acid oxidation. AA treatment induced phosphorylation of AMPK and acetyl CoA carboxylase. Taken together, results suggest that AA ameliorates liver fatty acid metabolism dysfunction in diabetic models, likely through inhibiting fatty acid synthesis and promoting fatty acid oxidation by activating AMPK signaling pathways.