University of Groningen Regulatory enzymes of mitochondrial B-oxidation as targets for treatment of the metabolic syndrome Bijker-Schreurs, Marijke 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: 2009 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Schreurs, M. (2009). Regulatory enzymes of mitochondrial B-oxidation as targets for treatment of the metabolic syndrome Groningen: 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: 17-12-2017
Regulatory enzymes of mitochondrial β-oxidation as targets for treatment of the metabolic syndrome Marijke Schreurs
Research The studies described in this these were conducted within the Graduate School for Drug Exploration (GUIDE), Center for Liver, Digestive and Metabolic Diseases (CLDS), Department of Pediatrics, University Medical Center Groningen, University of Groningen, The Netherlands Funding The studies described in this thesis were supported by grant 2003.00.009 from the Dutch Diabetes Foundation, Amersfoort, The Netherlands Printing of this thesis was financially supported by Diabetesfonds Nederland, Amersfoort, The Netherlands Rijksuniversiteit Groningen, Groningen, The Netherlands Universitair Medisch Centrum Groningen, Groningen, The Netherlands Graduate School for Drug Exploration (GUIDE) Nederlandse Vereniging voor Hepatologie, Haarlem, The Netherlands Sigma-tau BV, Utrecht, The Netherlands Colofon Cover Marijke Schreurs & Johan Gibcus Layout Johan Gibcus ISBN 978-90-367-3860-6 Printer Gildeprint, Enschede Marijke Schreurs 2009
Regulatory enzymes of mitochondrial β-oxidation as targets for treatment of the metabolic syndrome Proefschrift ter verkrijging van het doctoraat in de Medische Wetenschappen aan de Rijksuniversiteit Groningen op gezag van de Rector Magnificus, dr. F. Zwarts, in het openbaar te verdedigen op woensdag 30 september 2009 om 16.15 uur door Marijke Schreurs geboren op 13 januari 1981 te Rotterdam
Promotor: Copromotor: Prof. dr. F. Kuipers Dr. D.J. Reijngoud Beoordelingscommissie: Prof. dr. A.K. Groen Prof. dr. M.H. Hofker Prof. dr. R.J.A. Wanders
Paranimfen: Anke Laskewitz Maaike Oosterveer
Contents Chapter 1 General introduction 9 Chapter 2 Fish oil potentiates high-fat diet-induced peripheral insulin resistance in mice 19 Chapter 3 Pharmacological inhibition of the acetyl-coa carboxylase system by CP-640186 improves peripheral insulin sensitivity in mice 39 Chapter 4 Soraphen, an inhibitor of the acetyl-coa carboxylase system, improves peripheral insulin sensitivity in mice fed a high fat diet 55 Chapter 5 Inhibition of carnitine palmitoyltransferase 2 by aminocarnitine prevents ketoacidosis in a mouse model of type I diabetes: a metabolomic approach 73 Chapter 6 Mice heterozygous for CPT1a-deficiency show only subtle changes in fat and glucose metabolism upon feeding a high fat diet 89 Chapter 7 Regulatory enzymes of mitochondrial β-oxidation as targets for treatment of the metabolic syndrome 105 Chapter 8 English Summary 130 Nederalandse samenvatting 131 Dankwoord 133 Curriculum Vitae 134