Laboratory of Diabetes and Nutrition, Tohoku University, New Industry Creation Hatcher Center, Sendai, Miyagi, Japan.
Front Endocrinol (Lausanne). 2023 Jan 27;14:1080790. doi: 10.3389/fendo.2023.1080790. eCollection 2023.
Farnesoid X receptor (FXR) and Takeda G protein-coupled Receptor 5 (TGR5), the intestinal bile acid (BA) receptors, regulate the gut-derived hormones including fibroblast growth factor 15/19 (FGF15/19) and serotonin (5-hydrooxytryptamine, 5-HT). Here we show that ingestion of whey protein isolate, a milk protein, significantly decreased expression of heteromeric organic solute transporter Ostα and Ostβ, which is the basolateral BA transporter in the enterocyte, and increased the expression of FXR and FGF15 in C57BL6J mouse ileum and plasma FGF15 levels. In addition, the ingestion of whey protein isolate significantly suppressed expression of hepatic cholesterol-7α hydroxylase (CYP7A1), which induces the primary BA synthesis, bile salt export pump (BSEP) and sodium-taurocholate cotransporting polypeptide (NTCP), which are the key transporters for the BA excretion and uptake in the liver, and genes involved in gluconeogenesis, 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 TGR5, glucagon-like peptide 1 (GLP-1), and tryptophan hydroxylase1 (Tph1) in the small intestine, leading to decreases in plasma 5-HT and insulin levels. On the other hand, ingestion of the soy protein β-conglycinin significantly increased the expression of Ostα and Ostβ, and decreased the expression of FGF15 in the ileum and plasma FGF15 levels, leading to the increases in expression of hepatic CYP7A1, BSEP, NTCP, and genes involved in gluconeogenesis, and the primary BAs in the liver. Moreover, ingestion of β-conglycinin significantly increased the expression of intestinal TGR5, GLP-1, and Tph1, leading to increases in plasma 5-HT and insulin levels. These findings suggest that whey protein and β-conglycinin have opposite effects on intestinal FGF15 and 5-HT secretion in mice.
法尼醇 X 受体 (FXR) 和 Takeda G 蛋白偶联受体 5 (TGR5)，即肠道胆汁酸 (BA) 受体，调节肠道衍生的激素，包括成纤维细胞生长因子 15/19 (FGF15/19) 和血清素 (5-羟色胺，5-HT)。在这里，我们发现乳清蛋白分离物（一种牛奶蛋白）的摄入显著降低了肠细胞基底外侧 BA 转运体异质有机溶质转运蛋白 Ostα 和 Ostβ 的表达，并增加了 C57BL6J 小鼠回肠和血浆 FGF15 水平的 FXR 和 FGF15 的表达。此外，乳清蛋白分离物的摄入显著抑制了肝脏胆固醇-7α羟化酶 (CYP7A1) 的表达，该酶诱导主要 BA 合成，胆汁盐输出泵 (BSEP) 和牛磺胆酸钠共转运蛋白 (NTCP)，这是肝脏中 BA 排泄和摄取的关键转运体，以及参与糖异生的基因，并降低了肝脏中的初级 BAs，包括胆酸、牛磺胆酸、甘胆酸和牛磺鹅脱氧胆酸，与对照组相比。此外，乳清蛋白分离物的摄入显著降低了小肠中 TGR5、胰高血糖素样肽 1 (GLP-1) 和色氨酸羟化酶 1 (Tph1) 的表达，导致血浆 5-HT 和胰岛素水平降低。另一方面，大豆蛋白β-伴大豆球蛋白的摄入显著增加了 Ostα 和 Ostβ 的表达，并降低了回肠和血浆 FGF15 水平的 FGF15 表达，导致肝脏中 CYP7A1、BSEP、NTCP 和参与糖异生的基因以及肝脏中初级 BAs 的表达增加。此外，β-伴大豆球蛋白的摄入显著增加了肠道 TGR5、GLP-1 和 Tph1 的表达，导致血浆 5-HT 和胰岛素水平升高。这些发现表明，乳清蛋白和β-伴大豆球蛋白对小鼠肠道 FGF15 和 5-HT 分泌具有相反的作用。
