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

Full text not available from this repository.

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:
CreatorsEmailORCIDORCID Put Code
Franko, AndrasUNSPECIFIEDorcid.org/0000-0003-0485-5439UNSPECIFIED
von Kleist-Retzow, Juergen-ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neschen, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wu, MoyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schommers, PhilippUNSPECIFIEDorcid.org/0000-0003-3375-6800UNSPECIFIED
Boese, MarlenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kunze, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hartmann, UrsulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanchez-Lasheras, CarmenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stoehr, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huntgeburth, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brodesser, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Irmler, MartinUNSPECIFIEDorcid.org/0000-0003-3169-479XUNSPECIFIED
Beckers, JohannesUNSPECIFIEDorcid.org/0000-0001-7874-3822UNSPECIFIED
de Angelis, Martin HrabeUNSPECIFIEDorcid.org/0000-0002-7898-2353UNSPECIFIED
Paulsson, MatsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schubert, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiesner, Rudolf J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
RESPIRATORY-CHAIN; GENE-EXPRESSION; NONALCOHOLIC STEATOHEPATITIS; OXIDATIVE-PHOSPHORYLATION; LIPID-METABOLISM; OBESITY; DEFICIENCIES; DYSFUNCTION; HOMEOSTASIS; IMPAIRMENTMultiple languages
Gastroenterology & HepatologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/44261

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item