MiR-34a regulates the glucose metabolism of Blunt snout bream (Megalobrama amblycephala) fed high-carbohydrate diets through the mediation of the Sirt1/FoxO1 axis

Abstract To investigate the regulatory effect of miR-34a on the sirtuin 1(sirt1) / forkhead box O 1 (foxo1) axis in Megalobrama amblycephala under high carbohydrate metabolism, M. amblycephala fish were fed either a control or a high glucose diet for eight weeks. Metabolic models of the high glucose group, normal glucose group, miR-34a inhibition group, and miR-34a overexpression group were constructed using miR-34a inhibitor and miR-34a mimic injection (where appropriate) in M. amblycephala . The results showed that the hepatic expression of SIRT1 was decreased by the high glucose diet after eight weeks, which promoted the expression of foxo1a . Additionally, hepatic pepck and g6pase expression were upregulated, thereby promoting gluconeogenesis. The upregulation of pparα increased the expression of lipid metabolic enzymes such as fas , lps , and acc ; therefore, excessive glycogen was deposited as lipid in the adipose tissue. Furthermore, we found that SIRT1 expression increased following miR-34a inhibitor injection, activating foxo1a expression levels, reducing hepatic gluconeogenesis, decreasing hepatic glycogen accumulation, and accelerating hepatic fat decomposition and fatty acid synthesis. In a nutrient metabolic homeostatic state, injection of miR-34a mimics promoted the expression of foxo1a and pepeck , enhanced fat metabolism and fatty acid synthesis, and inhibited SIRT1 protein expression. These results revealed that miR-34a mediates regulation of metabolic enzymes related to hepatic glucose and lipid metabolism by targeting SIRT1/FoxO1 in M. amblycephala under high carbohydrate diet.