Research Unit of Internal Medicine, Biocenter Oulu, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, POB 5000, University of Oulu, FI-90014 Oulu, Finland.
Research Unit of Biomedicine, Biocenter Oulu, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, POB 5000, University of Oulu, FI-90014 Oulu, Finland.
Cells. 2020 Nov 9;9(11):2445. doi: 10.3390/cells9112445.
Pregnane X receptor (PXR) activation has been found to regulate glucose and lipid metabolism and affect obesity in response to high-fat diets. PXR also modulates vascular tone. In fact, PXR appears to regulate multiple components of metabolic syndrome. In most cases, the effect of PXR action is harmful to metabolic health, and PXR can be hypothesized to play an important role in metabolic disruption elicited by exposure to endocrine-disrupting chemicals. The majority of the data on the effects of PXR activation on metabolic health come from animal and cell culture experiments. However, randomized, placebo-controlled, human trials indicate that the treatment with PXR ligands impairs glucose tolerance and increases 24-h blood pressure and heart rate. In addition, plasma 4β-hydroxycholesterol (4βHC), formed under the control of PXR in the liver, is associated with lower blood pressure in healthy volunteers. Furthermore, 4βHC regulates cholesterol transporters in peripheral tissues and may activate the beneficial reverse HDL cholesterol transport. In this review, we discuss the current knowledge on the role of PXR and the PXR-4βHC axis in the regulation of components of metabolic syndrome.
孕烷 X 受体 (PXR) 的激活被发现可调节葡萄糖和脂质代谢，并影响肥胖对高脂肪饮食的反应。PXR 还调节血管张力。事实上，PXR 似乎调节代谢综合征的多个组成部分。在大多数情况下，PXR 作用的影响对代谢健康是有害的，可以假设 PXR 在接触内分泌干扰化学物质引起的代谢紊乱中发挥重要作用。关于 PXR 激活对代谢健康影响的大多数数据来自动物和细胞培养实验。然而，随机、安慰剂对照、人体试验表明，PXR 配体的治疗会损害葡萄糖耐量，并增加 24 小时血压和心率。此外，肝脏中 PXR 控制下形成的血浆 4β-羟胆固醇 (4βHC) 与健康志愿者的血压较低有关。此外，4βHC 调节外周组织中的胆固醇转运蛋白，并可能激活有益的反向 HDL 胆固醇转运。在这篇综述中，我们讨论了目前关于 PXR 及其 PXR-4βHC 轴在调节代谢综合征成分中的作用的知识。
