Kømurcu, KS, Wilhelmsen, I, Thorne, JL orcid.org/0000-0002-3037-8528 et al. (4 more authors) (2023) Mass Spectrometry Reveals that Oxysterols are Secreted from Non-Alcoholic Fatty Liver Disease Induced Organoids. The Journal of Steroid Biochemistry and Molecular Biology, 232. 106355. ISSN 0960-0760
Abstract
Oxysterols are potential biomarkers for liver metabolism that are altered under disease conditions such as non-alcoholic fatty liver disease (NAFLD). We here apply sterolomics to organoids used for disease modeling of NAFLD. Using liquid chromatography-mass spectrometry with on-line sample clean-up and enrichment, we establish that liver organoids produce and secrete oxysterols. We find elevated levels of 26-hydroxycholesterol, an LXR agonist and the first oxysterol in the acidic bile acid synthesis, in medium from steatotic liver organoids compared to untreated organoids. Other upregulated sterols in medium from steatotic liver organoids are dihydroxycholesterols, such as 7α,26–dihydroxycholesterol, and 7α,25-dihydroxycholesterol. Through 26-hydroxycholesterol exposure to human stem cell-derived hepatic stellate cells, we observe a trend of expressional downregulation of the pro-inflammatory cytokine CCL2, suggesting a protective role of 26-hydroxycholesterol during early-phased NAFLD disease development. Our findings support the possibility of oxysterols serving as NAFLD indicators, demonstrating the usefulness of combining organoids and mass spectrometry for disease modeling and biomarker studies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2023 Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
Keywords: | Liquid Chromatography; NAFLD; Mass Spectrometry; Organoids; Oxysterols |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Environment (Leeds) > School of Food Science and Nutrition (Leeds) > FSN Chemistry and Biochemistry (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Jul 2023 14:35 |
Last Modified: | 04 Jul 2023 14:35 |
Status: | Published |
Publisher: | Elsevier |
Identification Number: | 10.1016/j.jsbmb.2023.106355 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:201120 |