Metabolomics: One Powerful Tool for the Understanding of Xenobiotic Receptors

Abstract

Copyright: © 2012 Li F. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Xenobiotic receptors including members of the nuclear and soluble transcription factor superfamilies, can mediate the metabolic response of organism to the chemical environment. Upon activation, these receptors function to regulate numerous physiological processes, including the metabolism of xenobiotic pharmaceuticals and carcinogens as well as the control of endogenous lipid, cholesterol, energy and inflammatory pathways. For example, the peroxisome proliferator activated receptor (PPAR) α involves in the metabolism and transport of fatty acid; the farnesoid X receptor (FXR) is responsible for control of bile acid metabolism and transport; the pregnane X receptor (PXR) is a key regulator of drug transport and metabolism. A number of clinical drugs can perform their efficacy through the activation of xenobiotic receptors, including hypolipidemic fibrate drugs, ursodeoxycholic acid (UCDA), and rifaximin. However, in many cases, activation of xenobiotic receptors can lead to toxic and carcinogenic responses. Over past 20 years, the transgenic mouse model, including knockout and humanized mice, was widely used to explore the function of xenobiotic receptors. Despite numerous studies are conducted in xenobiotic receptors, the mechanism about how these receptors perform their function in response to xenobiotic challenge and their roles in the development of various diseases, such as cancer and diabetes, still remains unclear.