Transcript Title and contents - Rijksuniversiteit Groningen

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)
Groningen University Institute for Drug Exploration (GUIDE)
Cholesterol, bile acid and triglyceride
metabolism intertwined
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
door 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
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
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
Chapter 4
45
Chapter 5
Transintestinal Cholesterol Excretion Can Drive
Massive Cholesterol Elimination in Mice
63
Chapter 6
Transintestinal and Biliary Cholesterol Secretion
Both Contribute to Macrophage Reverse Cholesterol
Transport in Rats
General Discussion
91
101
I
II
III
IV
V
VI
VII
113
125
129
131
139
145
147
Chapter 7
Appendices
References
Abbreviations
Contributing Authors & Affiliations
Nederlanse Samenvatting
Dankwoord/Acknowledgements
Biografie/Biography
List of Publications
7