Universität zu Köln

Franko, Andras ORCID: 0000-0003-0485-5439, von Kleist-Retzow, Juergen-Christoph, Neschen, Susanne, Wu, Moya, Schommers, Philipp ORCID: 0000-0003-3375-6800, Boese, Marlen, Kunze, Alexander, Hartmann, Ursula, Sanchez-Lasheras, Carmen, Stoehr, Oliver, Huntgeburth, Michael, Brodesser, Susanne, Irmler, Martin ORCID: 0000-0003-3169-479X, Beckers, Johannes ORCID: 0000-0001-7874-3822, de Angelis, Martin Hrabe ORCID: 0000-0002-7898-2353, Paulsson, Mats, Schubert, Markus and Wiesner, Rudolf J. (2014). Liver adapts mitochondrial function to insulin resistant and diabetic states in mice. J. Hepatol., 60 (4). S. 816 - 824. AMSTERDAM: ELSEVIER SCIENCE BV. ISSN 1600-0641

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Abstract

Background & Aims: To determine if diabetic and insulin-resistant states cause mitochondrial dysfunction in liver or if there is long term adaptation of mitochondrial function to these states, mice were (i) fed with a high-fat diet to induce obesity and T2D (HFD), (ii) had a genetic defect in insulin signaling causing whole body insulin resistance, but not full blown T2D (IR/IRS-1(+/-) mice), or (iii) were analyzed after treatment with streptozocin (STZ) to induce a T1D-like state. Methods: Hepatic lipid levels were measured by thin layer chromatography. Mitochondrial respiratory chain (RC) levels and function were determined by Western blot, spectrophotometric, oxygen consumption and proton motive force analysis. Gene expression was analyzed by real-time PCR and microarray. Results: HFD caused insulin resistance and hepatic lipid accumulation, but RC was largely unchanged. Livers from insulin resistant IR/IRS-1(+/-) mice had normal lipid contents and a normal RC, but mitochondria were less well coupled. Livers from severely hyperglycemic and hypoinsulinemic STZ mice had massively depleted lipid levels, but RC abundance was unchanged. However, liver mitochondria isolated from these animals showed increased abundance and activity of the RC, which was better coupled. Conclusions: Insulin resistance, induced either by obesity or genetic manipulation and steatosis do not cause mitochondrial dysfunction in mouse liver. Also, mitochondrial dysfunction is not a prerequisite for liver steatosis. However, severe insulin deficiency and high blood glucose levels lead to an enhanced performance and better coupling of the RC. This may represent an adaptation to fuel overload and the high energy-requirement of an unsuppressed gluconeogenesis. (C) 2013 European Association for the Study of the Liver. Published by Elsevier B. V. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Franko, Andras UNSPECIFIED orcid.org/0000-0003-0485-5439 UNSPECIFIED von Kleist-Retzow, Juergen-Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Neschen, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Wu, Moya UNSPECIFIED UNSPECIFIED UNSPECIFIED Schommers, Philipp UNSPECIFIED orcid.org/0000-0003-3375-6800 UNSPECIFIED Boese, Marlen UNSPECIFIED UNSPECIFIED UNSPECIFIED Kunze, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Ursula UNSPECIFIED UNSPECIFIED UNSPECIFIED Sanchez-Lasheras, Carmen UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoehr, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED Huntgeburth, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Brodesser, Susanne UNSPECIFIED UNSPECIFIED UNSPECIFIED Irmler, Martin UNSPECIFIED orcid.org/0000-0003-3169-479X UNSPECIFIED Beckers, Johannes UNSPECIFIED orcid.org/0000-0001-7874-3822 UNSPECIFIED de Angelis, Martin Hrabe UNSPECIFIED orcid.org/0000-0002-7898-2353 UNSPECIFIED Paulsson, Mats UNSPECIFIED UNSPECIFIED UNSPECIFIED Schubert, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesner, Rudolf J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-442619
DOI:	10.1016/j.jhep.2013.11.020
Journal or Publication Title:	J. Hepatol.
Volume:	60
Number:	4
Page Range:	S. 816 - 824
Date:	2014
Publisher:	ELSEVIER SCIENCE BV
Place of Publication:	AMSTERDAM
ISSN:	1600-0641
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RESPIRATORY-CHAIN; GENE-EXPRESSION; NONALCOHOLIC STEATOHEPATITIS; OXIDATIVE-PHOSPHORYLATION; LIPID-METABOLISM; OBESITY; DEFICIENCIES; DYSFUNCTION; HOMEOSTASIS; IMPAIRMENT Multiple languages Gastroenterology & Hepatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44261