Fig. 9: 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.