Abstract | OBJECTIVE: METHODS: Wildtype and PXR knockout male mice were fed high-fat diet to induce obesity and metabolic dysfunction. PXR was activated with pregnenolone-16α-carbonitrile. Glucose metabolism, hepatosteatosis, insulin signaling, glucose uptake, liver glycogen, plasma and liver metabolomics, and liver, white adipose tissue, and muscle transcriptomics were investigated. RESULTS: CONCLUSIONS:
Obesity and PXR activation by chemical exposure have a synergistic effect on NAFLD development. To support liver fat accumulation the PXR activation reorganizes glucose metabolism that seemingly improves systemic glucose metabolism. This implies that obese individuals, already predisposed to metabolic diseases, may be more susceptible to harmful metabolic effects of PXR-activating drugs and environmental chemicals.
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Authors | Mikko Karpale, Outi Kummu, Olli Kärkkäinen, Marko Lehtonen, Juha Näpänkangas, Uta M Herfurth, Albert Braeuning, Jaana Rysä, Jukka Hakkola |
Journal | Molecular metabolism
(Mol Metab)
Vol. 76
Pg. 101779
(10 2023)
ISSN: 2212-8778 [Electronic] Germany |
PMID | 37467962
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2023 The Authors. Published by Elsevier GmbH.. All rights reserved. |
Chemical References |
- Pregnane X Receptor
- Glucose
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Topics |
- Mice
- Animals
- Male
- Non-alcoholic Fatty Liver Disease
- Pregnane X Receptor
- Mice, Obese
- Insulin Resistance
- Obesity
(metabolism)
- Glucose
(metabolism)
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