Duodenal-jejunal bypass increases intraduodenal bile acids and upregulates duodenal SIRT1 expression in high-fat diet and streptozotocin-induced diabetic rats

Figure 1 Effects of duodenal-jejunal bypass on metabolic parameters. A: Body weight of rats; B: Food intake of rats; C: Fasting blood glucose of rats; D: Oral glucose tolerance test (OGTT) at 2 wk after operation; E: OGTT at 8 wk after operation; F: Area under the curve (AUC) of OGTT at 2 and 8 wk after operation; G: Intraperitoneal pyruvate tolerance test (ipPTT) at 2 wk after operation; H: ipPTT at 8 wk after operation; I: AUC_ipPTT at 2 and 8 wk after operation. ^cP < 0.001 duodenal-jejunal bypass (DJB) vs sham group by the Student’s t-test or post-hoc Bonferroni’s multiple comparison test. ^dP < 0.001, DJB vs sham group by mixed model ANOVA. AUC_OGTT: Area under the curve of oral glucose tolerance test; AUC_ipPTT: Area under the curve of intraperitoneal pyruvate tolerance test; OGTT: Oral glucose tolerance test; ipPTT: Intraperitoneal pyruvate tolerance test; DJB: Duodenal-jejunal bypass.

Figure 2 Duodenal-jejunal bypass increased serum and intraduodenal total bile acids and activated bile acids signaling in the duodenal mucosa. A: Fasting and postprandial serum total bile acids (TBAs) at 2 and 8 wk after operation; B: Intraluminal TBAs in the descending and horizontal duodenum at 8 wk after operation; C and D: Expression of key genes involved in BA signaling pathway in the mucosa of descending and horizontal duodenum; E: Cyclic adenosine 3’,5’-monophosphate concentration in the duodenal mucosa. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001 duodenal-jejunal bypass vs sham group. DJB: Duodenal-jejunal bypass; TBAs: Total bile acids; FXR: Farnesoid X receptor; SHP: Small heterodimer partner; TGR5: Takeda G-protein-coupled receptor 5; cAMP: Cyclic adenosine 3’,5’-monophosphate.

Figure 3 Duodenal-jejunal bypass increased SIRT1 expression and promoted phosphorylation of AMPK in the duodenal mucosa. A: Western blot images of SIRT1, phosphorylated AMPK (p-AMPK), and total AMPK (t-AMPK) in the descending duodenum; B and C: The relative intensity of SIRT1 and p-AMPK/t-AMPK in the descending duodenum; D: Western blot images of SIRT1, p-AMPK, and t-AMPK in the horizontal duodenum; E and F: The relative intensity of SIRT1 and p-AMPK/t-AMPK in the horizontal duodenum. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001 duodenal-jejunal bypass vs sham group. p-AMPK: Phosphorylated AMPK; t-AMPK: Total AMPK; DJB: Duodenal-jejunal bypass.

Figure 4 Activation of farnesoid X receptor and Takeda G-protein-coupled receptor 5 increased SIRT1 and promoted phosphorylation of AMPK in rat small intestine epithelial IEC-6 cells. A and B: Effects of farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5) activation on SIRT1, AMPK, and key genes involved in BA signaling pathway; C: Western blot images of SIRT1, phosphorylated AMPK (p-AMPK), and total AMPK (t-AMPK) in IEC-6 cells after FXR activation; D and E: The relative intensity of SIRT1 and p-AMPK/t-AMPK in IEC-6 cells after FXR activation. F: Western blot images of SIRT1, p-AMPK, and t-AMPK in IEC-6 cells after TGR5 activation; G and H: The relative intensity of SIRT1 and p-AMPK/t-AMPK in IEC-6 cells after TGR5 activation. ^aP < 0.05, ^bP < 0.01, ^cP < 0.001 GW4064 or INT-777 vs control group. p-AMPK: Phosphorylated AMPK; t-AMPK: Total AMPK; FXR: Farnesoid X receptor; SHP: Small heterodimer partner; TGR5: Takeda G-protein-coupled receptor 5.