Fig 2: Effect of Ileocolonic delivery of conjugated bile acids (IC-CBAS) on bile acid pathways in patients with obesity and type 2 diabetes. (a) Total faecal bile acids (circles, baseline; and squares, treatment); (b) delta total fecal bile acids and (c) delta primary faecal bile acids; (d) delta total faecal bile acids by group (circles, placebo; and squares, IC-CBAS); (e) delta conjugated faecal bile acids, (f) delta postprandial serum bile acids, (g) delta C4, (h) delta fasting FGF19, (i) delta fasting total cholesterol, (j) delta fasting cLDL, (k) correlation between ∆ weight and ∆ faecal bile acids; (l) correlation between ∆ fructosamine with ∆ faecal bile acids after 1-month treatment with IC-CBAS, and (m). correlation between ∆ postprandial GLP-1 at 45 min with ∆ faecal bile acids after 1-month treatment with IC-CBAS Data are presented as mean±SEM. Wilcoxon, *p<0·05, ** p<0·01. ANCOVA, ^p<0·05, (Figs. a–j).

Fig 3: Schematic diagram of the working model.The role of hepatic TH signaling in the regulation of glucose homeostasis. In hepatocytes, activation of TRβ by T3 shapes the BA composition and increases the levels of non-12α-OH FXR-antagonistic BAs, which are shown in red, through suppressing the CYP8B1 expression. In L-cells, inactivation of FXR signaling by non-12α-OH FXR-antagonistic BAs increases the GLP-1 production, thereby potentiating insulin secretion. CHOL, cholesterol.

Fig 4: Relative expression of Proglucagon mRNA (gray bar) and GLP-1 protein (black bar) in colonic mucosa of a random selection of control fed and FOS fed rats. mRNA and protein levels were normalized to Actin levels. Expression is shown as means ± SEM (n = 7). **p < 0.01, ***P < 0.001

Fig 5: Modulation of GLP-1 production by CaMKKβ/CaMKIV and mTOR signaling activity in STC-1 cells.(A–C) STC-1 cells were transfected with GFP, CaMKKβ or CaMKIV plasmids for 48 hr. (A) Gcg mRNA levels in STC-1 cells. (B) GLP-1 concentrations in culture medium. (C) Whole-cell extracts underwent western blot with indicated antibodies. (D–F) STC-1 cells were treated with CaMKKβ inhibitor STO-609 (10 μmol/L) for 24 hr. (D) Gcg mRNA levels in STC-1 cells. (E) GLP-1 concentrations in culture medium. (F) Whole-cell extracts underwent western blot with indicated antibodies. (G–I) STC-1 cells were pretreated with Rapamycin (50 nmol/L) for 1 hr, then treated with Yoda1 (5 μmol/L) for 24 hr. (G) Gcg mRNA levels in STC-1 cells. (H) GLP-1 concentrations in the culture medium. (I) Whole-cell extracts underwent western blot with indicated antibodies. Data are represented as mean ± SEM and are representative of six biological replicates. Significance was determined by Student’s t test for comparison between two groups, and by one-way ANOVA for comparison among three groups or more, *p<0.05, **p<0.01, ***p<0.001. Figure 7—source data 1.PDF file containing original western blots for Figure 7C, F and I, indicating the relevant bands and treatments. Figure 7—source data 2.Original files for western blot analysis displayed in Figure 7C, F and I. Figure 7—source data 3.Original data for Figure 7.