Mass spectrometry reveals that oxysterols are secreted from non-alcoholic fatty liver disease induced organoids

Kristina Sæterdal Kømurcu; Ingrid Wilhelmsen; James L Thorne; Stefan Krauss; Steven Ray Wilson; Aleksandra Aizenshtadt; Hanne Røberg-Larsen

doi:10.1016/j.jsbmb.2023.106355

Mass spectrometry reveals that oxysterols are secreted from non-alcoholic fatty liver disease induced organoids

J Steroid Biochem Mol Biol. 2023 Sep:232:106355. doi: 10.1016/j.jsbmb.2023.106355. Epub 2023 Jun 26.

Authors

Kristina Sæterdal Kømurcu¹, Ingrid Wilhelmsen², James L Thorne³, Stefan Krauss², Steven Ray Wilson¹, Aleksandra Aizenshtadt⁴, Hanne Røberg-Larsen⁵

Affiliations

¹ Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, 0315 Oslo, Norway; Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.
² Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway; Department of Immunology and Transfusion Medicine, Oslo University Hospital, Rikshospitalet, P.O. box 4950 Nydalen, Oslo, Norway.
³ School of Food Science and Nutrition, University of Leeds, Leeds LS2 9JT, United Kingdom.
⁴ Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway.
⁵ Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, 0315 Oslo, Norway; Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110 Blindern, 0317 Oslo, Norway. Electronic address: hannero@kjemi.uio.no.

PMID: 37380087
DOI: 10.1016/j.jsbmb.2023.106355

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.

Keywords: Liquid Chromatography; Mass Spectrometry; NAFLD; Organoids; Oxysterols.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Mass Spectrometry
Non-alcoholic Fatty Liver Disease*
Oxysterols* / metabolism
Sterols

Substances

Oxysterols
Sterols