Inhibition of Farnesoid X Receptor Rescues Fat Depression Induced by Dietary Berberine in Grass Carp, Ctenopharyngodon Idella

Berberine (BBR) depresses lipid accumulation in fish, but the mechanism remains unknown. In this study, we hypothesize FXR signaling participates in this physiological process of grass carp. Three diets, namely the control, BBR (1.0 g/kg), and BBR + Gly-β-MCA (an FXR inhibitor) were formulated to feed juvenile grass carp (9.90 ± 0.07) for 8 weeks. Fish fed BBR presented significantly lower IPF index, hepatic TG and TC contents, as well as whole body lipid levels, whereas these were rescued by Gly-β-MCA. Serum TG and HDL-c contents were significantly decreased in fish fed BBR compared to those in the control. The serum ALT activity, combined with the TG, TC, HDL-c, and LDL-c concentrations were all significantly increased in fish fed BBR + Gly-β-MCA than those fed BBR. Dietary BBR significantly increased the mRNA and protein expression of FXR, decreased the mRNA level of FGF19 in the intestine, whereas these were reversed by Gly-β-MCA. In the hepatopancreas, the inhibitor recovered the suppression of the CYP7A1, CYP8B1, and CYP27A1 expression induced by dietary BBR. Fish fed BBR showed significantly lower mRNA expression of SREBP-1c and FAS, whereas these two genes were all up-regulated in response to inhibitor. Dietary BBR increased the gene expression of PPARα, ATGL, CPT-1, which were all abolished by dietary Gly-β-MCA treatment. Fish fed BBR and BBR + Gly-β-MCA showed significantly lower total OTUs, ACE index, chao 1 index, and simpson index of the gut microbiota. Overall, our results demonstrate that inhibition of FXR leads to the rescue of lipid suppression induced by dietary BBR in grass carp.