Ingestion of whey protein and beta-conglycinin exerts opposite effects on intestinal FGF15-mediated hepatic bile acid synthesis in mice.

Abstract

Farnesoid X receptor (FXR), a BA receptor, and fibroblast growth factor 15 (FGF15) regulate enterohepatic circulation of BAs, glucose, and lipid metabolism. Here we show that ingestion of whey protein isolate, a milk protein, significantly increased plasma FGF15 levels and the expression of FXR and FGF15 in mouse ileum. In addition, ingestion of whey protein isolate significantly suppressed the expression of hepatic cholesterol-7α hydroxylase (CYP7A1), which induces BA synthesis, and decreased the primary BAs, including cholic acid, taurocholic acid, glycocholic acid, and taurochenodeoxycholic acid in the liver compared with controls. Moreover, ingestion of whey protein isolate significantly decreased the expression of Takeda G protein-coupled Receptor 5 (TGR5), glucagon-like peptide 1 (GLP-1), and tryptophan hydroxylase1 (Tph1) in the small intestine, and plasma serotonin and insulin levels. On the other hand, ingestion of the soy protein β-conglycinin significantly decreased the expression of FGF15 in the ileum and plasma FGF15 levels, leading to increased expression of hepatic CYP7A1 and BA synthesis. Moreover, ingestion of β-conglycinin significantly increased the expression of intestinal TGR5, GLP-1, and Tph1, and plasma 5-HT and insulin levels. These findings suggest that whey protein and β-conglycinin have opposite effects on intestinal FGF15-mediated hepatic BA synthesis and intestinal serotonin secretion in mice.