University of Groningen Gut microbiota and nuclear receptors in bile acid and lipid metabolism Out, Carolien 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: 2014 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Out, C. (2014). Gut microbiota and nuclear receptors in bile acid and lipid metabolism: bile acids, more than soaps [S.l.]: [S.n.] 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: 09-01-2019
Gut microbiota and nuclear receptors in bile acid and lipid metabolism Bile acids, more than soaps Carolien Out
The research described in this thesis was conducted at the Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. The studies described in this thesis were financially supported by the Junior Scientific Masterclass (JSM) Groningen. The author gratefully acknowledges the financial support for printing this thesis by: Groningen University Institute for Drug Exploration (GUIDE) Rijksuniversiteit Groningen (RuG) Universitair Medisch Centrum Groningen (UMCG) Greiner Bio-One B.V. Research Diet Services B.V. Cover design: Carolien Koopman Layout: Ridderprint BV, Ridderkerk, The Netherlands Printed by: Ridderprint BV, Ridderkerk, The Netherlands ISBN: 978-90-5335-902-0 Copyright Carolien Out, 2014. All rights reserved. No part of this thesis may be reproduced, distributed, stored in a retrieval system, or transmitted in any form or by any means without prior permission of the author.
Gut microbiota and nuclear receptors in bile acid and lipid metabolism Bile acids, more than soaps Proefschrift 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 26 november 2014 om 14.30 uur door Carolien Out geboren op 5 april 1988 te Zwolle
Promotores Prof. dr. A.K. Groen Prof. dr. H.J. Verkade Beoordelingscommissie Prof. dr. B. Staels Prof. dr. B.M. Bakker Prof. dr. U.H.W. Beuers
The problem is not the problem. The problem is your attitude about the problem. Do you understand? Captain Jack Sparrow. Half the solution to any problem lies in defining it Dr. Phil.
Paranimfen Anne Marijn van der Graaf Marije Boesjes
Contents Chapter 1 Rationale, general introduction and thesis outline 9 Chapter 2 Bile acid sequestrants: more than simple resins 31 Chapter 3 Liver receptor homolog-1 is critical for adequate upregulation of Cyp7a1 gene transcription and bile salt synthesis during bile salt sequestration 55 Chapter 4 LRH-1 plays a central role in hepatic triglyceride metabolism 77 Chapter 5 Gut microbiota inhibit ASBT-dependent intestinal bile acid reabsorption via GATA4 99 Chapter 6 Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity. 121 Chapter 7 Prednisolone increases enterohepatic cycling of bile acids by induction of Asbt and promotes reverse cholesterol transport 141 Chapter 8 General discussion Future perspectives Conclusions 161 175 177 Chapter 9 Summary Nederlandse samenvatting voor niet-ingewijden Dankwoord / Acknowledgement Biografie / Biography List of publications 189 191 197 203 205