Figure 5.

Enterohepatic action of FXR and FATP5. Role of FXR and FATP5 in synthesis, transport, and enterohepatic circulation of BAs and the effects of steroidal and non-steroidal agonists on the activity of the same. In the liver, activation of FXR by agonists induces SHP to inhibit cyp7a1 gene transcription that further allows the liver to downregulate the BA synthesis in response to maintaining a constant BA pool. The TG level is reduced by SHP acting on SREBP-1c. BAs are secreted via BSEP into the gallbladder and reabsorbed via ASBT in terminal ileum enterocytes. Here, they bind and activate FXR, which stimulates production and secretion of FGF15/19 into the portal circulation. BAs activate FXR in the intestine to induce FGF15/19 which is transported to hepatocytes to activate FGFR4, which further activates a signaling pathway involving MAP kinases and causes repression of cyp7a1 transcription, thus downregulating BA synthesis. After this the OSTα/β-mediated secretion into the portal circulation, BAs are taken up by the liver via NTCP, completing the enterohepatic cycle. The FATP5 involved in the uptake of fatty acids and the conjugation of BAs in the liver. The FATP5 conjugates the BA by BA-CoA enzymatic activity. The BAs inhibit the uptake of long-chain fatty acid in FATP5 dependent manner and inhibits the TG level in the liver and maintain the lipid homeostasis in the liver. The endogenous ligand and the synthetic ligand for both the receptors are given in the figure.