Hepatocyte nuclear factor 4alpha regulation of bile acid and drug metabolism.

Title

Hepatocyte nuclear factor 4alpha regulation of bile acid and drug metabolism.

Creator

Chiang John Y L

Publisher

Expert opinion on drug metabolism & toxicology

Date

2009
2009-02

Description

The hepatocyte nuclear factor 4alpha (HNF4alpha) is a liver-enriched nuclear receptor that plays a critical role in early morphogenesis, fetal liver development, liver differentiation and metabolism. Human HNF4alpha gene mutations cause maturity on-set diabetes of the young type 1, an autosomal dominant non-insulin-dependent diabetes mellitus. HNF4alpha is an orphan nuclear receptor because of which the endogenous ligand has not been firmly identified. The trans-activating activity of HNF4alpha is enhanced by interacting with co-activators and inhibited by corepressors. Recent studies have revealed that HNF4alpha plays a central role in regulation of bile acid metabolism in the liver. Bile acids are required for biliary excretion of cholesterol and metabolites, and intestinal absorption of fat, nutrients, drug and xenobiotics for transport and distribution to liver and other tissues. Bile acids are signaling molecules that activate nuclear receptors to control lipids and drug metabolism in the liver and intestine. Therefore, HNF4alpha plays a central role in coordinated regulation of bile acid and xenobiotics metabolism. Drugs that specifically activate HNF4alpha could be developed for treating metabolic diseases such as diabetes, dyslipidemia and cholestasis, as well as drug metabolism and detoxification.

Subject

Humans; Animals; Gene Expression Regulation; Lipid Metabolism; Liver/metabolism; Signal Transduction/physiology; Bile Acids and Salts/*metabolism; Genetic Predisposition to Disease; Mutation; Pharmaceutical Preparations/*metabolism; Hepatocyte Nuclear Factor 4/genetics/*metabolism

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

137–147

Issue

2

Volume

5

Citation

Chiang John Y L, “Hepatocyte nuclear factor 4alpha regulation of bile acid and drug metabolism.,” NEOMED Bibliography Database, accessed April 16, 2021, https://neomed.omeka.net/items/show/4983.

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