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The farnesoid X receptor (FXR) is a nuclear receptor expressed in the liver, small intestine, kidneys, and adrenals. In mouse liver, FXR is bound to thousands of genomic DNA binding sites. Conformational changes induced by bile acid binding to pre-bound FXR leads to increased expression of a variety of genes. These changes lead to decreased intracellular bile acid concentrations through multiple mechanisms including decreased bile acid synthesis from cholesterol, decreased hepatocellular uptake and increased secretion into bile. Activated FXR also modulates the expression of genes responsible for lipid and glucose metabolism. One of the other genes induced by activated FXR is a small heterodimeric partner (SHP), a protein that represses expression of specific genes. The effects of pharmacologically modulating FXR activation in humans is only beginning to be explored with the hopes of favorably altering lipid and glucose metabolism to address the vascular and metabolic complications of obesity and diabetes.


Brent A Neuschwander-Tetri. Farnesoid x receptor agonists: what they are and how they might be used in treating liver disease. Current gastroenterology reports. 2012 Feb;14(1):55-62

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PMID: 22094889

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