University of Groningen Intestinal nuclear receptor signaling in cystic fibrosis Doktorova, Marcela 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: 2017 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Doktorova, M. (2017). Intestinal nuclear receptor signaling in cystic fibrosis. [Groningen]: University of 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: 15-04-2019
Intestinal nuclear receptor signaling in cystic fibrosis Marcela Doktorova Demmin
Cover design: Ridderprint B.V., Ridderkerk, The Netherlands Layout: Ridderprint B.V., Ridderkerk, The Netherlands Printed by Ridderprint B.V., Ridderkerk, The Netherlands ISBN: 978-94-6299-689-2 2017 Marcela Doktorova Demmin. All rights reserved. No parts of this thesis may be reproduced, stored or transmitted, in any form or by any means, without permission of the author.
,Intestinal nuclear receptor signaling in cystic fibrosis,, PhD thesis Intestinal nuclear receptor signaling in cystic fibrosis,to obtain the degree of PhD at the University of Groningen on the authority of the Rector Magnificus Prof. E. Sterken and in accordance with the decision by the College of Deans. This thesis will be defended in public on Wednesday 1 November 2017 at 11.00 hours PhD thesis by Marcela Demmin born on 11 September 1988 in Bratislava, Slovakia to obtain the degree of PhD at the University of Groningen on the authority of the Rector Magnificus Prof. E. Sterken and in accordance with the decision by the College of Deans. This thesis will be defended in public on Wednesday 1 November 2017 at 11.00 hours by Marcela Demmin born on 11 September 1988 in Bratislava, Slovakia
Supervisors Prof. H.J. Verkade Prof. J.W. Jonker Assessment Committee Prof. F. Kuipers Prof. G.H. Koppelman Prof. R.H.J. Houwen Paranymphs Marleen Schonewille Ivo Pieter van de Peppel The research described in this thesis was conducted at the Department of Pediatrics, Section Molecular Metabolism and Nutrition, University Medical Center Groningen, The Netherlands. This project was funded by the Dutch Cystic Fibrosis Foundation (Nederlandse Cystic Fibrosis Stichting) and by the Jan Kornelis de Cock Stichting. The printing of this dissertation was financially supported by: The University of Groningen The University Medical Center Groningen the Groningen University Institute for Drug Exploration (GUIDE)
Table of contents Chapter 1 General introduction and scope of the thesis 7 Chapter 2 Intestinal PPARδ protects against diet-induced obesity, insulin resistance and dyslipidemia 27 Chapter 3 Impaired intestinal farnesoid X receptor signaling in cystic fibrosis mice 51 Chapter 4 CFTR potentiator ivacaftor restores FGF19 regulated bile acid homeostasis in cystic fibrosis patients with a G551D mutation 93 Chapter 5 Laxative treatment ameliorates bile acid metabolism and FXR/ FGF15 signaling in mice with cystic fibrosis 107 Chapter 6 ASBT is a major determinant of intestinal cholesterol transport 123 Chapter 7 General discussion 143 Appendices Summary in English 163 Sammenvatting in het Nederlands 163 Acknowledgements 167 List of publications 171