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. Author manuscript; available in PMC: 2015 Sep 2.
Published in final edited form as: Drug Metab Rev. 2013 Feb;45(1):48–59. doi: 10.3109/03602532.2012.748793

Figure 3.

Figure 3

Model for the gut-liver axis that involves the FGF15/19-signaling mechanism. Endocrine actions of FGF15. Expression of the gene encoding FGF15 is induced in the small intestine by bile acids acting on the FXR/RXRα heterodimer. Subsequently, FGF15 is secreted into the enterohepatic circulation to act in an endocrine manner by binding a receptor on hepatocytes called FGFR4. The activated FGFR4 receptor signals the liver to repress CYP7A1 expression and activity. The CYP7A1 enzyme is the rate-limiting step in the synthesis of bile acids from cholesterol. In this manner, FGF15 (FGF19 in humans) suppresses de novo synthesis of bile acids from cholesterol through a mechanism that requires SHP. The extent to which this mechanism functions to downregulate drug-and bile-acid–transporter proteins in hepatocytes is currently unknown, but is a likely fruitful area of future research.