Adaptations of the 3T3-L1 adipocyte lipidome to defective ether lipid catabolism upon Agmo knockdown.

3T3-L1 adipocyte differentiation adipocytes alkylglycerol monooxygenase ether lipids lipid metabolism lipidomics lipids lipolysis and fatty acid metabolism triacylglycerol

Journal

Journal of lipid research
ISSN: 1539-7262
Titre abrégé: J Lipid Res
Pays: United States
ID NLM: 0376606

Informations de publication

Date de publication:
06 2022
Historique:
received: 02 12 2021
revised: 28 04 2022
accepted: 29 04 2022
pubmed: 11 5 2022
medline: 29 6 2022
entrez: 10 5 2022
Statut: ppublish

Résumé

Little is known about the physiological role of alkylglycerol monooxygenase (AGMO), the only enzyme capable of cleaving the 1-O-alkyl ether bond of ether lipids. Expression and enzymatic activity of this enzyme can be detected in a variety of tissues including adipose tissue. This labile lipolytic membrane-bound protein uses tetrahydrobiopterin as a cofactor, and mice with reduced tetrahydrobiopterin levels have alterations in body fat distribution and blood lipid concentrations. In addition, manipulation of AGMO in macrophages led to significant changes in the cellular lipidome, and alkylglycerolipids, the preferred substrates of AGMO, were shown to accumulate in mature adipocytes. Here, we investigated the roles of AGMO in lipid metabolism by studying 3T3-L1 adipogenesis. AGMO activity was induced over 11 days using an adipocyte differentiation protocol. We show that RNA interference-mediated knockdown of AGMO did not interfere with adipocyte differentiation or affect lipid droplet formation. Furthermore, lipidomics revealed that plasmalogen phospholipids were preferentially accumulated upon Agmo knockdown, and a significant shift toward longer and more polyunsaturated acyl side chains of diacylglycerols and triacylglycerols could be detected by mass spectrometry. Our results indicate that alkylglycerol catabolism has an influence not only on ether-linked species but also on the degree of unsaturation in the massive amounts of triacylglycerols formed during in vitro 3T3-L1 adipocyte differentiation.

Identifiants

pubmed: 35537527
pii: S0022-2275(22)00055-4
doi: 10.1016/j.jlr.2022.100222
pmc: PMC9192799
pii:
doi:

Substances chimiques

Ethers 0
Phospholipids 0
Triglycerides 0
Ether 0F5N573A2Y

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

100222

Subventions

Organisme : Austrian Science Fund FWF
ID : P 30800
Pays : Austria

Informations de copyright

Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.

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Auteurs

Sabrina Sailer (S)

Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.

Katharina Lackner (K)

Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.

Mia L Pras-Raves (ML)

Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands; Bioinformatics Laboratory, Department of Epidemiology & Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.

Eric J M Wever (EJM)

Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands; Bioinformatics Laboratory, Department of Epidemiology & Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.

Jan B van Klinken (JB)

Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.

Adriaan D Dane (AD)

Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands; Bioinformatics Laboratory, Department of Epidemiology & Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands.

Stephan Geley (S)

Institute of Molecular Pathophysiology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.

Jakob Koch (J)

Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.

Georg Golderer (G)

Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.

Gabriele Werner-Felmayer (G)

Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.

Markus A Keller (MA)

Institute of Human Genetics, Medical University of Innsbruck, Innsbruck, Austria.

Werner Zwerschke (W)

Division of Cell Metabolism and Differentiation Research, Research Institute for Biomedical Aging Research, University of Innsbruck, Innsbruck, Austria.

Frédéric M Vaz (FM)

Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry and Pediatrics, Emma Children's Hospital, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands; Core Facility Metabolomics, Amsterdam UMC Location University of Amsterdam, Amsterdam, The Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism, Inborn Errors of Metabolism, Amsterdam, The Netherlands.

Ernst R Werner (ER)

Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.

Katrin Watschinger (K)

Institute of Biological Chemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: katrin.watschinger@i-med.ac.at.

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Classifications MeSH