Role of signalling systems in the effects of dietary factors on the expression of mammalian CYPs

Abstract

Changes in mammalian diets alter the hepatic expression of CYP drug-metabolising enzymes and endobiotic oxidases. Thus, dietary constituents may significantly influence the duration of action of chemicals in tissues. Recent improvements in the mechanistic information on the regulation of constitutive and inducible expression of CYPs has facilitated our understanding as to how dietary factors modulate expression. Altered regulation appears to occur either by direct activation of transcription factors or by indirect modulation of signal transduction pathways. For example, dietary lipid directly activates PPAR-α, or other nuclear hormone receptors, to elicit CYP induction, and vitamin A deficiency downregulates the growth hormone-responsive CYP2C11 by perturbing Janus kinase-signal transducers and activators of transcription signalling. This article focuses on the present understanding of the regulation of CYP genes by dietary nutrients.

Keywords::

• cytochrome P450
• gene regulation
• growth hormone
• Jak-STAT
• lipotrope deficiency
• nuclear receptors
• vitamin A deficiency

Acknowledgement

Work in this laboratory is funded by grants from the National Health and Medical Research Council of Australia.