Farnesoid X Receptor-Mediated Bile Acids Regulation in Cholestasis.

Abstract

The main process, for the elimination of cholesterol from the human body, involves the alteration of cholesterol into bile acid (BA), by the liver. The farnesoid X receptor (FXR), a member of the nuclear receptor superfamily, is essential for the regulation of BA, glucose, and lipid metabolism. It is largely found in the liver, intestines, kidney, and adrenal glands, and to a smaller degree in the heart and adipose tissue. The binding locations, of the FXR, are in close proximity to formerly undisclosed target genes, with distinctive activities associated with transcriptional regulators, autophagy, apoptosis, hypoxia, inflammation, RNA processing, and a number of cellular signaling pathways. The preservation of BA homeostasis, by the FXR, entails the direct stimulation of the expression of the small heterodimer partner in the liver, and the fibroblast growth factor 15/19 (FGF15/FGF19) in the intestine, which impedes the activity of enzymes associated with hepatic BA synthesis, including cytochrome P450 7A1 (Cyp7a1). This investigation delves into the role of the FXR in terms of BA metabolism regulation, as well as its role in the pathophysiologic activity of cholestasis.