San-Huang-Tang protects obesity/diabetes induced NAFLD by upregulating PGC-1α/PEPCK signaling in obese and galr1 knockout mice models

Ethnopharmacological relevance: San-Huang-Tang (ST), a classic prescription, has been clinically used to cure diabetes and diabetes-associated metabolic disorders. Established studies have reported that ST can alleviate inflammation, obesity, hyperglycemia and insulin resistance. Aim of the study: To the best of our knowledge, here, we reported for the first time the underlying mechanistic therapeutic efficacy of the ST against nonalcoholic fatty liver disease (NAFLD) in high-fat induced obese and galr1-deficient diabetic mice. Materials and methods: The obese and gair1-deficient mice were treated with ST at a dose of 10 g/kg every day for three weeks. Then food intake, body weight and insulin resistance indexes were measured. Western blotting, qRT-PCR, and plasma biochemical analyses were applied. Results: ST reduced food intake, body weight, blood glucose level and insulin resistance, improved glucose tolerance in obese and galr1 -deficient mice. Mechanistically, we confirmed that ST protected against NAFLD through activation of PGC-1 alpha and its downstream signaling pathways as shown by the attenuated hepatic adipogenesis and lipid accumulation, increased hepatic fatty acid oxidation, regulated plasma lipid parameters, and increased energy expenditure and metabolic function in fat and muscle. Conclusions: Reduction in food intake produced by ST may contribute to the observed metabolic effects. Our findings strongly suggest that ST might be a potential novel therapeutic drug against obesity/diabetes-induced NAFLD and other metabolic disorders.