5-Methoxyflavone Targets CYP1A1 To Alleviate Hfd-Induced Disorders Of Hepatic Glucose And Lipid Metabolism

Fatty liver disease is a common nutritional metabolic disease and the most common non-infectious cause of mortality in poultry animals.When hepatic lipogenesis and fatty acid oxidation are imbalanced,it leads to excessive deposition of triglycerides in the liver,which in turn leads to reduced production performance and even death.Fatty liver disease due to disorders of glycolipid metabolism is becoming an increasingly common problem in poultry farming,which is seriously hampering the development of the industry.However,to date,proven treatments are still lacking.5-Methoxyflavone,a flavonoid extracted from Kaempferia minor,a plant in the ginger family,acts as a central nervous system sedative,an inhibitor of DNA polymerase-β and a β-amyloid neuroprotective agent.In the present study,the role of 5-methoxyflavonoid in glucolipid metabolism and fatty liver disease was determined for the first time.5-Methoxyflavone(5-MF),a flavonoid extracted from kaempferia parviflora,a member of the ginger family,is a central nervous system sedative,an inhibitor of DNA polymerase-beta and a neuroprotective agent against β-amyloid toxicity.In the current study,the role of 5-methoxyflavone in glucolipid metabolism and fatty liver disease was determined for the first time.5-Methoxyflavone(5-MF)is a flavonoid extracted from kaempferia parviflora,a plant of the ginger family,with sedative effects on the central nervous system,an inhibitor of DNA polymerase-β and a neuroprotective agent against β-amyloid toxicity.In the current study,the role of 5-methoxyflavone in glucolipid metabolism and fatty liver disease was determined for the first time.This study focused on the induction of OA/PA(oleic acid/palmitic acid)in Hep G2 cells to establish an in vitro high-fat model.And 40 μM of 5-methoxyflavone was added to study its regulation of glycolipid metabolism in hepatocytes and mechanism.C57BL/6J mice were used as in vivo animal models and randomly divided into three groups of six mice each:(1)normal chow group(NC group),(2)high-fat diet group(HFD group),(3)high-fat diet with 50 mg/kg of 5-methoxyflavone(HFD+5-MF group)to investigate the effect of 5-methoxyflavone on glucolipid metabolism.The results showed that 5-methoxyflavone not only reduced triglyceride levels and cholesterol content in the liver,but also alleviated lipid peroxidation by enhancing the antioxidant capacity of the liver,thereby alleviating oxidative stress.In addition,5-methoxyflavone improved insulin resistance and glucose tolerance in mice induced by high-fat diet,further achieving the effect of regulating glucose metabolism.Moreover,5-methoxyflavonoid-treated mice showed enhanced exercise and increased energy expenditure.Finally,molecular simulations and cellular experiments determined that 5-methoxyflavone exerted the above functions by targeting inhibition of CYP1A1.This study not only found the ameliorative effect of 5-methoxyflavone on the fatty liver disease but also provided an important reference for the prevention and treatment of fatty liver and related nutritional metabolic diseases in livestock.