Digestive System > Liver

Bile Acids as Hormones

Bile acids have long been known to facilitate digestion and absorption of lipids in the small intestine. Recently, it has been demonstrated that bile acids also function as hormones that bind to nuclear receptors and, through that mechanism, modulate expression of proteins involved in cholesterol homeostasis. More generally, there is considerable evidence that bile acids act in conjunction with insulin to promote the metabolism of nutrients in the liver.

Several orphan nuclear receptors have been shown to bind bile acids (cholic and chenodeoxycholic acids), including the farsenoid X receptor (FRX), the LXRalpha receptor and the CPA receptor. Further, the resulting bile acid-receptor complexes have been shown capable of binding to promoter regions of specific genes and either stimulating or suppressing their transcription. In essence, bile salts can function as steroid hormones.

Studies on the binding of bile acids to the FRX receptor has provided two examples of how bile salts affect cholesterol homeostasis by altering gene expression:

These two actions suggest that in the whole animal, elevated blood levels of bile acids leads both to diminished synthesis of new bile acids and enhanced recycling of those that exist. Undoubtedly, additional endocrine actions of bile salts will be delineated through current and future studies of this newly discovered system.

References and Reviews

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