University of Oulu

Hassani-Nezhad-Gashti, F., Kummu, O., Karpale, M. et al. Nutritional status modifies pregnane X receptor regulated transcriptome. Sci Rep 9, 16728 (2019).

Nutritional status modifies pregnane X receptor regulated transcriptome

Saved in:
Author: Hassani-Nezhad-Gashti, Fatemeh1,2; Kummu, Outi1,2; Karpale, Mikko1,2;
Organizations: 1Research Unit of Biomedicine, Pharmacology and Toxicology, University of Oulu, Oulu, Finland
2Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
3School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2 MB)
Persistent link:
Language: English
Published: Springer Nature, 2019
Publish Date: 2020-03-04


Pregnane X receptor (PXR) regulates glucose and lipid metabolism, but little is known of the nutritional regulation of PXR function. We investigated the genome wide effects of the nutritional status on the PXR mediated gene regulation in the liver. Mice were treated with a PXR ligand pregnenolone 16α-carbonitrile (PCN) for 4 days and subsequently either fasted for 5 hours or after 4-hour fast treated with intragastric glucose 1 hour before sample collection. Gene expression microarray study indicated that PCN both induced and repressed much higher number of genes in the glucose fed mice and the induction of multiple well-established PXR target genes was potentiated by glucose. A subset of genes, including bile acid synthesis gene Cyp8b1, responded in an opposite direction during fasting and after glucose feeding. PXR knockout abolished these effects. In agreement with the Cyp8b1 regulation, PCN also modified the bile acid composition in the glucose fed mice. Contribution of glucose, insulin and glucagon on the observed nutritional effects was investigated in primary hepatocytes. However, only mild impact on PXR function was observed. These results show that nutritional status modifies the PXR regulated transcriptome both qualitatively and quantitatively and reveal a complex crosstalk between PXR and energy homeostasis.

see all

Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 9
Issue: 1
Article number: 16728
DOI: 10.1038/s41598-019-53101-9
Type of Publication: A1 Journal article – refereed
Field of Science: 317 Pharmacy
Funding: The study was financially supported by the grants from the Academy of Finland (Grants 286743 and 276747), the Novo Nordisk Foundation (Grants NNF14OC0010653 and NNF15OC0015846) and the Diabetes research Foundation.
Academy of Finland Grant Number: 286743
Detailed Information: 286743 (Academy of Finland Funding decision)
Copyright information: © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit