Novel functions of PXR in cardiometabolic disease
#MMPMID26924429
Zhou C
Biochim Biophys Acta
2016[Sep]; 1859
(9
): 1112-1120
PMID26924429
show ga
Cardiometabolic disease emerges as a worldwide epidemic and there is urgent need
to understand the molecular mechanisms underlying this chronic disease. The
chemical environment to which we are exposed has significantly changed in the
past few decades and recent research has implicated its contribution to the
development of many chronic human diseases. However, the mechanisms of how
exposure to chemicals contributes to the development of cardiometabolic disease
are poorly understood. Numerous chemicals have been identified as ligands for the
pregnane X receptor (PXR), a nuclear receptor functioning as a xenobiotic sensor
to coordinately regulate xenobiotic metabolism via transcriptional regulation of
xenobiotic-detoxifying enzymes and transporters. In the past decade, the function
of PXR in the regulation of xenobiotic metabolism has been extensively studied by
many laboratories and the role of PXR as a xenobiotic sensor has been
well-established. The identification of PXR as a xenobiotic sensor has provided
an important tool for the study of new mechanisms through which xenobiotic
exposure impacts human chronic diseases. Recent studies have revealed novel and
unexpected roles of PXR in modulating obesity, insulin sensitivity, lipid
homeostasis, atherogenesis, and vascular functions. These studies suggest that
PXR signaling may contribute significantly to the pathophysiological effects of
many known xenobiotics on cardiometabolic disease in humans. The discovery of
novel functions of PXR in cardiometabolic disease not only contributes to our
understanding of "gene-environment interactions" in predisposing individuals to
chronic diseases but also provides strong evidence to inform future risk
assessment for relevant chemicals. This article is part of a Special Issue
entitled: Xenobiotic nuclear receptors: New Tricks for An Old Dog, edited by Dr.
Wen Xie.
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