title: Liver mitochondrial function in ZDF rats during the early stages of diabetes disease.
abstract: The aim of this study was to characterize the early alterations of the liver mitochondrial function in ZDF (fa/fa) rats that develop diabetes compared to that of their lean counterparts ZDF (fa/+). Liver mitochondrial function was examined in 11- and 14-week-old ZDF (fa/fa) and ZDF lean (fa/+) rats. Oxygen consumption, H2O2 release, calcium retention capacity (CRC), membrane potential, membrane fluidity, and fatty acid composition were analyzed. State 3 oxygen consumption with palmitoyl-carnitine increases between 11 and 14 weeks of age in lean but not in diabetic animals. This response was not seen with other substrates, suggesting that the use of fatty acids is impaired in diabetic rats. H2O2 release was lower in 14-week-old ZDF (fa/fa) rats as compared to ZDF lean (fa/+). These changes were not associated with differences in enzymatic activities of the respiratory complexes, suggesting regulatory mechanisms independent of their expression levels. Membrane fluidity and composition analyses show only slight effects linked to diabetes progression. The most salient feature was a reduction in CRC in the presence of CsA, an effect reflecting PTP dysregulation. Our data suggest few changes of mitochondrial function in ZDF fa/fa rats. At the age of 11 weeks, liver mitochondria have mainly a reduced effect of CsA on CRC.
authors: Facultés de médecine Charles Mérieux Lyon-Sud et Rockfeller, INSERM U-1060 Laboratoire CarMeN Université Lyon 1, INRA 1235, INSA de Lyon, Lyon, France European Center For Nutrition and Health, Centre Hospitalier Lyon Sud, Pierre-Bénite, France Guillaume.vial@inserm.fr.
authors: Guillaume
authors: G
authors: Vial
authors: Laboratoire de Bioénergétique Fondamentale et Appliquée (LBFA) et SFR Biologie Environnementale et Systémique (BEeSy), INSERM U-1055, Grenoble, France Joseph Fourier University, Grenoble, France.
authors: Marie
authors: M
authors: Le Guen
authors: Laboratoire de Bioénergétique Fondamentale et Appliquée (LBFA) et SFR Biologie Environnementale et Systémique (BEeSy), INSERM U-1055, Grenoble, France Joseph Fourier University, Grenoble, France Grenoble University Hospital, Grenoble, France.
authors: Frédéric
authors: F
authors: Lamarche
authors: Centre de Recherche Cardio-Thoracique de Bordeaux - CRCTB - LIRYC Université de Bordeaux 2, Bordeaux, INSERM U-1045 Hôpital Xavier Arnozan, Bordeaux, Bordeaux, France.
authors: Dominique
authors: D
authors: Detaille
authors: Laboratoire de Bioénergétique Fondamentale et Appliquée (LBFA) et SFR Biologie Environnementale et Systémique (BEeSy), INSERM U-1055, Grenoble, France.
authors: Cécile
authors: C
authors: Cottet-Rousselle
authors: Laboratoire de Bioénergétique Fondamentale et Appliquée (LBFA) et SFR Biologie Environnementale et Systémique (BEeSy), INSERM U-1055, Grenoble, France Unité de Nutrition Humaine, INRA, UMR 1019 Clermont Université Université d'Auvergne, Clermont-Ferrand, France.
authors: Luc
authors: L
authors: Demaison
authors: Laboratoire de Bioénergétique Fondamentale et Appliquée (LBFA) et SFR Biologie Environnementale et Systémique (BEeSy), INSERM U-1055, Grenoble, France Joseph Fourier University, Grenoble, France.
authors: Isabelle
authors: I
authors: Hininger-Favier
authors: Facultés de médecine Charles Mérieux Lyon-Sud et Rockfeller, INSERM U-1060 Laboratoire CarMeN Université Lyon 1, INRA 1235, INSA de Lyon, Lyon, France.
authors: Pierre
authors: P
authors: Theurey
authors: Institut de Recherche Biomédicale des Armées-Unité des Risques Technologiques Emergents, Brétigny sur Orge, France.
authors: David
authors: D
authors: Crouzier
authors: Institut de Recherche Biomédicale des Armées-Unité des Risques Technologiques Emergents, Brétigny sur Orge, France.
authors: Jean-Claude
authors: JC
authors: Debouzy
authors: Laboratoire de Bioénergétique Fondamentale et Appliquée (LBFA) et SFR Biologie Environnementale et Systémique (BEeSy), INSERM U-1055, Grenoble, France Joseph Fourier University, Grenoble, France.
authors: Hervé
authors: H
authors: Dubouchaud
authors: Laboratoire de Bioénergétique Fondamentale et Appliquée (LBFA) et SFR Biologie Environnementale et Systémique (BEeSy), INSERM U-1055, Grenoble, France Joseph Fourier University, Grenoble, France Grenoble University Hospital, Grenoble, France.
authors: Éric
authors: É
authors: Fontaine
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000503:physiopathology; D004578:Electron Spin Resonance Spectroscopy; D005434:Flow Cytometry; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species
keywords: Diabetes; ZDF; mitochondria; oxidative phosphorylation