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University of Groningen Applying lipidomics strategies to study lipid metabolic diseases Zhang, Wenxuan

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University of Groningen

Applying lipidomics strategies to study lipid metabolic diseases

Zhang, Wenxuan

DOI:

10.33612/diss.169407826

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2021

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Zhang, W. (2021). Applying lipidomics strategies to study lipid metabolic diseases. University of Groningen. https://doi.org/10.33612/diss.169407826

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Applying lipidomics strategies to

study lipid metabolic diseases

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The research described in this thesis was carried out at the Department of Pediatrics, Center for Liver, Digestive and Metabolic Disease, University Medical Center Groningen, Groningen, the Netherlands.

The studies described in this thesis were financially supported by the SysMed Grant from the University Medical Center Groningen.

The printing of this dissertation was financially supported by: University of Groningen (RuG)

University Medical Center Groningen (UMCG)

Groningen University Institute of Drug Exploration (GUIDE) Cover design: Guus Gijben | proefschrift-aio.nl

Book layout: Guus Gijben | proefschrift-aio.nl Printed by: proefschrift-aio.nl

© Wenxuan Zhang, 2021

All rights reserved. No part of this doctoral thesis may be reproduced, stored in a retrieval system or transmitted in any form or by any means without permission of the author.

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Applying lipidomics strategies to study

lipid metabolic diseases

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans. This thesis will be defended in public on

Monday 10 May 2021 at 12.45 hours

by

Wenxuan Zhang

born on 22 September 1990 in Xi’an, China

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Supervisors

Prof. F. Kuipers Prof. R.P.H. Bischoff Prof. D.J. Reijngoud

Assessment Committee

Prof. F.J. van Spronsen Prof. J. Heeren

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Table of Content

Introduction - Chapter 1 9

Part I Evaluation of lipid extraction systems

Chapter 2 Omics technology: lipidomics and its pitfalls during the preanalytical stage

27

Chapter 3 One- vs two-phase extraction: re-evaluation of sample preparation procedures for untargeted lipidomics in plasma samples

55

Part II Application of lipidomics to disease-related studies

Chapter 4 The plasma lipidome of individuals with extreme levels of LDL-c

79

Chapter 5 The role of hepatic fatty-acid oxidation during cold stress: remodeling of whole body energy and lipid metabolism in Acadm-knockout mice.

105

Chapter 6 Low LRH-1 expression in mice promotes development of Western-type diet-induced steatohepatitis and liver fibrosis

Multi-omics integration reveals a critical role of LRH-1 in adequate adaptation of hepatic lipid metabolism to nutrient overload

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Part III Discussion

Chapter 7 General discussion 171

Appendix Summary 186 Nederlandse samenvatting 190 中文摘要 194 Acknowledgement 196 Curriculum vitae 200 List of Publications 202

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