Identification of a Nuclear Receptor for Bile Acids

Abstract

Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter. These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport.

Fibrates suppress chenodeoxycholic acid-induced RANTES expression through inhibition of NF-κB activation

“…Hirano,et al page 13 receptor, farnesoid X receptor (Wang et al, 1999;Makishima et al, 1999;Parks et al, 1999); farnesoid X receptor binds to DNA as a heterodimer with retinoid X receptor, recognizing an inverted hexanucleotide repeat separated by a single base (an IR-1 motif) (Forman et al, 1995). Although no IR-1 element has been identified in the RANTES promoter, further study should examine whether interaction between farnesoid X receptor and PPAR is related to inhibitory effects of fibrates on chenodeoxycholic acid-induced RANTES gene expression.…”

Quantification of the 15 major human bile acids and their precursor 7α-hydroxy-4-cholesten-3-one in serum by liquid chromatography–tandem mass spectrometry

“…Moreover, their emulsifying properties are essential for digestion of dietary fat and lipophilic vitamins. In the last decade, bile acids were additionally discovered to be natural ligands of the farnesoid X receptor (FXR) [1][2][3], a nuclear transcription factor through which they regulate their own biosynthesis via a negative feedback. Moreover, it is now well established that FXR activation by bile acids results in the regulation of various genes involved not solely in bile acid homeostasis but also in cholesterol, triglyceride and glucose metabolism [4][5][6][7][8][9].…”

Effects of nuclear receptor FXR on the regulation of liver lipid metabolism in patients with non-alcoholic fatty liver disease

“…In 1999, some groups found that bile acids were the natural ligands of FXR, which is since known as the BAR [12,13]. FXR is expressed abundantly in liver, intestines, kidneys, etc.…”