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

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.