Intestinal farnesoid X receptor mediates the effect of dietary berberine on lipid accumulation in grass carp (Ctenopharyngodon idella)

Berberine (BBR) suppresses lipid accumulation in fish, but mechanisms underlying this effect remain poorly understood. The aim of this study was to test the hypothesis that intestinal farnesoid X receptor (FXR) signaling is involved in this physiological process. Thus, juvenile grass carp (9.90 ± 0.07 g) were fed experimental diets (control, 0.1% BBR, and 0.1% BBR + Gly-β-MCA [an intestine-specific FXR inhibitor]) for 8 weeks. Dietary BBR significantly reduced intraperitoneal fat, hepatic triglyceride (TG), total cholesterol (TC), and whole-body lipid levels, whereas additional supplementation with Gly-β-MCA restored these levels. Dietary BBR also significantly reduced serum TG and high-density lipoprotein cholesterol (HDL-c), and additional supplementation with Gly-β-MCA significantly increased serum alanine aminotransferase activity and levels of TG, TC, HDL-c, and low-density lipoprotein cholesterol. Dietary BBR significantly increased FXR mRNA and protein expression, as well as fibroblast growth factor 19 mRNA expression in the intestine, whereas additional supplementation with Gly-β-MCA reversed these trends. Gly-β-MCA also restored BBR-reduced hepatopancreatic cholesterol 7 alpha-hydroxylase, sterol 12α-hydroxylase, and sterol 27-hydroxylase expression, sterol-regulatory element binding proteins-1c and fatty acid synthase expression, and attenuated BBR-increased peroxisome proliferator activated receptor α, adipose triglyceride lipase, and carnitine palmitoyltransferase 1 expression. Both BBR and BBR + Gly-β-MCA diets significantly reduced the richness and diversity of the fish gut microbiota. The abundance of Firmicutes showed a significant negative correlation with the mRNA expression of FXR in the intestine. Overall, these findings indicate that FXR signaling is involved in lipid suppression induced by dietary BBR in grass carp.