Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathway.

Finn, Robert, Henderson, Colin, Scott, Claire and Wolf, Roland (2009) Unsaturated fatty acid regulation of cytochrome P450 expression via a CAR-dependent pathway. Biochemical Journal, 417 (1). pp. 43-54. ISSN 0264-6021

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Official URL: http://dx.doi.org/10.1042/BJ20080740

Abstract

The liver is responsible for key metabolic functions, including control of normal homoeostasis in response to diet and xenobiotic metabolism/detoxification. We have shown previously that inactivation of the hepatic cytochrome P450 system through conditional deletion of POR (P450 oxidoreductase) induces hepatic steatosis, liver growth and P450 expression. We have exploited a new conditional model of POR deletion to investigate the mechanism underlying these changes. We demonstrate that P450 induction, liver growth and hepatic triacylglycerol (triglyceride) homoeostasis are intimately linked and provide evidence that the observed phenotypes result from hepatic accumulation of unsaturated fatty acids, which mediate these phenotypes by activation of the nuclear receptor CAR (constitutive androstane receptor) and, to a lesser degree, PXR (pregnane X receptor). To our knowledge this is the first direct evidence that P450s play a major role in controlling unsaturated fatty acid homoeostasis via CAR. The regulation of P450s involved in xenobiotic metabolism by this mechanism has potentially significant implications for individual responses to drugs and environmental chemicals.

Item Type: Article
Additional Information: constitutive androstane receptor (CAR), cytochrome P450, linoleic acid, P450 oxidoreductase (POR), pregnane X receptor (PXR), steatosis.
Subjects: C700 Molecular Biology, Biophysics and Biochemistry
Department: Faculties > Health and Life Sciences > Applied Sciences
Depositing User: EPrint Services
Date Deposited: 13 May 2010 12:52
Last Modified: 01 Nov 2017 03:47
URI: http://nrl.northumbria.ac.uk/id/eprint/2573

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