Dietary berberine ameliorates glucose metabolism by regulating the FXR pathway in largemouth bass ( Micropterus salmoides )

Berberine (BBR) ameliorates glucose (GLU) metabolism in fish and growing evidences showed that the Farnesoid X receptor (FXR) is involved in the regulation of GLU metabolism in mammals, but the molecular mechanisms behind the effect remain unclear. Thus, this study aimed to investigate the regulated function of FXR on GLU metabolism in largemouth bass (Micropterus salmoides). Largemouth bass (133.7 +/- 1.43 g) were fed with five experimental diets (control, BBR (1 g/kg), GW4064 (FXR agonist GW4064, 0.1 g/kg), MCA (FXR inhibitor GlyMCA, 25 mg/kg), and BBR+MCA (1 g/kg BBR + 25 mg/kg MCA) for 50 days. The results showed that dietary BBR and GW4064 decreased serum GLU and increased serum total bile acid (TBA), whereas opposite effects were observed in the MCA and MCA+BBR groups. Similarly, dietary BBR and GW4064 improved hepatic histological morphology, whereas dietary MCA and MCA+BBR induced hepatic damage. Furthermore, dietary BBR positively influenced the composition of intestinal bile acid (BA) metabolites, as demonstrated by the decreased contents of beta-MCA and deoxycholic acid (DCA) and increased contents of taurodeoxycholic acid sodium salt (THCA), taurohyodeoxycholic acid sodium salt (THDCA) and cholic acid (CA), activating the FXR signal in intestine of largemouth bass. Consistently, dietary BBR and GW4064 increased intestinal mRNA levels of fxr and shp, whereas MCA supplementation reversed the trends. Moreover, dietary BBR and GW4064 enhanced the glycolysis by increasing the activity of HK and PK and promoted the glycogen synthesis by decreasing gsk3 beta expression and increasing gs expression. Additionally, dietary BBR increased the ratio of Firmicutes/Bacteroidetes and relative abundance of Lactobacillus, Faecalibacterium and Lactococcus lactis. Overall, these results indicated that BBR may improve GLU metabolism of largemouth bass by enhancing glycolysis and inhibiting gluconeogenesis due to the activation of FXR signal, contributing to the decrease of blood GLU level.