Bile Acids, the Farnesoid X Receptor FXR and Fat Metabolism

Bile acids are also natural ligands for the farnesoid X receptor (FXR), a receptor that belongs to the nuclear hormone receptor superfamily. The hydrophobic bile acid chenodeoxycholic acid (CDCA) is the most potent 

In vivo, FXR is expressed in white adipose tissue (WAT) with levels decreased in the WAT of dietary (high fat) and genetic objob mice) models of obesity.  

With respect to glycaemic parameters FXR-deficient mice (FXR ) show impaired glucose tolerance, whole-body glucose disposal and insulin resistance. FXR deficiency is also associated with impaired distal insulin signalling in muscle and WAT through reduced insulin-dependent AKT phosphorylation.  

Finally, dyslipidemia is a feature of FXR knockout mice levels of VLDL, LDL and HDL cholesterol and ApoB lipoproteins are increased concomitant with reduced clearance of HDL cholesteryl ester and elevated triglyceride and free fatty-acid levels.  

These data raise the possibility that targetted activation of FXR may also be a useful route to manage various aspects of the metabolic phenotype including type-2 diabetes, dyslipidemia and adipocyte function. 

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