University of Groningen Cholesterol, bile acid and triglyceride metabolism intertwined Schonewille, Marleen 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: 2016 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Schonewille, M. (2016). Cholesterol, bile acid and triglyceride metabolism intertwined [Groningen]: Rijksuniversiteit Groningen Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date: 11-02-2018
Cholesterol, bile acid and triglyceride metabolism intertwined Marleen Schonewille
The research described in this dissertation was carried out at the Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. The author gratefully acknowledges the financial support for printing this dissertation by: University Medical Center Groningen (UMCG) University of Groningen (RuG) Cholesterol, bile acid and triglyceride metabolism intertwined Groningen University Institute for Drug Exploration (GUIDE) Proefschrift Phenex Pharmaceuticals AG Dr. Falk Pharma Benelux B.V. Hartstichting Avanti Polar Lipids, Inc. and Dr. Walter A. Shaw ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen op gezag van de rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op woensdag 14 september 2016 om 12.45 uur Cover design: Marleen Schonewille Layout: Marleen Schonewille Printed by: Ridderprint BV, the Netherlands ISBN (printed): 978-90-367-9005-5 ISBN (digital): 978-90-367-9004-8 Copyright 2016 Marleen Schonewille. All rights reserved. No part of this publication may be reproduced, distributed, stored in a retrieval system or transmitted, in any form of by any means, without permission of the author and the publishers holding the copyrights of the articles door Marleen Schonewille geboren op 21 november 1987 te Hoogeveen
Promotor Prof. dr. A.K. Groen Beoordelingscommissie Prof. dr. B. Staels Prof. dr. K.N. Faber Prof. dr. E.S. Stroes Ik heb geen geheim van succes. Gewoon je best doen, iets leuk vinden en goede mensen om je heen verzamelen. Want alleen kun je niks en met z n allen kun je alles - Johan Cruijff Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged
Table of Contents Paranimfen Marcela Doktorova Aycha Bleeker Table of Contents Chapter 1 General Introduction 9 Chapter 2 Bile Salts in Control of Lipid Metabolism 19 Chapter 3 Chapter 4 Serum Triglyceride-Lowering Properties of Plant Sterols and Stanols Are Associated With Decreased Hepatic VLDL Secretion Statins Increase Hepatic Cholesterol Synthesis and Stimulate Fecal Cholesterol Elimination in Mice 31 45 Chapter 5 Transintestinal Cholesterol Excretion Can Drive Massive Cholesterol Elimination in Mice 63 Chapter 6 Transintestinal and Biliary Cholesterol Secretion 91 Both Contribute to Macrophage Reverse Cholesterol Transport in Rats Chapter 7 General Discussion 101 Appendices I References 113 II Abbreviations 125 III Contributing Authors & Affiliations 129 IV Nederlanse Samenvatting 131 V Dankwoord/Acknowledgements 139 VI Biografie/Biography 145 VII List of Publications 147 7