Novel functions of PXR in cardiometabolic disease

Publication date: Available online 26 February 2016
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Changcheng Zhou
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 contribute 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.



from #MedicinebyAlexandrosSfakianakis via xlomafota13 on Inoreader http://ift.tt/1QMLCZ8
via IFTTT