University of Oulu

Hukkanen, J.; Hakkola, J. PXR and 4β-Hydroxycholesterol Axis and the Components of Metabolic Syndrome. Cells 2020, 9, 2445.

PXR and 4β-hydroxycholesterol axis and the components of metabolic syndrome

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Author: Hukkanen, Janne1; Hakkola, Jukka2
Organizations: 1Research Unit of Internal Medicine, Biocenter Oulu, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, POB 5000, FI-90014 Oulu, Finland
2Research Unit of Biomedicine, Biocenter Oulu, Medical Research Center Oulu, University of Oulu and Oulu University Hospital, POB 5000, FI-90014 Oulu, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.1 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2020
Publish Date: 2020-11-25


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.

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Series: Cells
ISSN: 2073-4409
ISSN-E: 2073-4409
ISSN-L: 2073-4409
Volume: 9
Issue: 11
Article number: 2445
DOI: 10.3390/cells9112445
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: The original research of the authors has been financially supported by grants from the Diabetes Research Foundation, the Finnish Foundation for Cardiovascular Research, the Northern Finland Health Care Support Foundation, the Finnish Medical Foundation, the Academy of Finland (grants 286743 and 323706) and the Novo Nordisk Foundation (grants NNF14OC0010653 and NNF15OC0015846). The project EDCMET has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 825762.
EU Grant Number: (825762) EDCMET - Metabolic effects of Endocrine Disrupting Chemicals: novel testing METhods and adverse outcome pathways
Academy of Finland Grant Number: 286743
Detailed Information: 286743 (Academy of Finland Funding decision)
323706 (Academy of Finland Funding decision)
Copyright information: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (