Diabetologie und Stoffwechsel 2017; 12(S 01): S1-S84
DOI: 10.1055/s-0037-1601610
Vorträge
Development and Treatment of NAFLD
Georg Thieme Verlag KG Stuttgart · New York

Fatty liver and whole-body insulin resistance relate to myocardial lipotoxicity

E Alvarez Hernandez
1   Deutsches Diabetes Zentrum, Institut für Klinische Diabetologie, Düsseldorf, Germany
2   Deutsches Zentrum für Diabetesforschung (DZD e.V.), München-Neuherberg, Germany
,
T Jelenik
1   Deutsches Diabetes Zentrum, Institut für Klinische Diabetologie, Düsseldorf, Germany
2   Deutsches Zentrum für Diabetesforschung (DZD e.V.), München-Neuherberg, Germany
,
U Flögel
3   Universitätsklinikum Düsseldorf, Institut für Molekulare Kardiologie, Düsseldorf, Germany
,
M Rothe
1   Deutsches Diabetes Zentrum, Institut für Klinische Diabetologie, Düsseldorf, Germany
2   Deutsches Zentrum für Diabetesforschung (DZD e.V.), München-Neuherberg, Germany
,
I Rokitta
1   Deutsches Diabetes Zentrum, Institut für Klinische Diabetologie, Düsseldorf, Germany
2   Deutsches Zentrum für Diabetesforschung (DZD e.V.), München-Neuherberg, Germany
,
GI Shulman
4   Department of internal Medicine, Yale University School of Medicine, New Haven, United States
5   Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States
6   Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, United States
,
M Roden
1   Deutsches Diabetes Zentrum, Institut für Klinische Diabetologie, Düsseldorf, Germany
2   Deutsches Zentrum für Diabetesforschung (DZD e.V.), München-Neuherberg, Germany
7   Klinik für Endokrinologie und Diabetologie, Medizinische Fakultät, Heinrich Heine Universität, Düsseldorf, Germany
,
J Szendroedi
1   Deutsches Diabetes Zentrum, Institut für Klinische Diabetologie, Düsseldorf, Germany
2   Deutsches Zentrum für Diabetesforschung (DZD e.V.), München-Neuherberg, Germany
7   Klinik für Endokrinologie und Diabetologie, Medizinische Fakultät, Heinrich Heine Universität, Düsseldorf, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
05 May 2017 (online)

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    Introduction:

    Insulin resistance and non-alcoholic fatty liver (NAFL) associate with increased myocardial oxidative capacity, reactive oxygen species production and ischemia intolerance.

    Aim:

    To assess underlying mechanisms of myocardial changes in the context of whole body insulin resistance and NAFL, even in the absence of overt diabetes.

    Methods:

    We performed immunohistological assays, immunoblotting, proton magnetic resonance spectroscopy and liquid chromatography mass spectrometry in a non-diabetic murine model characterized by insulin resistance and NAFL due to adipose tissue-specific overexpression of sterol element binding protein 1c (IR-NAFL) and in wild type mice (CON). Results are stated as CON then IR-NAFL, mean ± standard error of mean.

    Results:

    IR-NAFL have decreased myocardial capillaries per mm2 (2656 ± 116 vs. 2146 ± 210, p = 0,001). IR-NAFL myocardium is not fibrotic and has a decreased water content (0,76 ± 0,001 vs. 0,74 ± 0,002 ml/mg, p < 0,001). Total myocardial lipids are doubled (1,8 ± 0,5 vs. 3,21 ± 1% water signal, p < 0,01), but triglycerides are unchanged compared to CON. Additionally, IR-NAFL present differences in lipid droplet arrangement and a trend towards decreased perilipin 2 expression. In IR-NAFL membrane 18:1/18:1 diacylglycerol (DAG) content is increased (98 ± 11,3mmol/g vs. 198 ± 7,6, p < 0,001), as is protein kinase C (PKC) membrane: cytosol ratio (0,2 ± 0,01 vs. 0,5 ± 0,04 arbitrary units (AU), p < 0,0001), membrane glucose transporter 4 expression is decreased by 55% (0,05 ± 0,006 vs. 0,02 ± 0,001 AU, p < 0,001). No differences were observed in CCAAT-enhancer-binding homologous protein (CHOP) expression.

    Conclusions:

    NAFL and insulin resistance already relate to myocardial DAG-PKC induced lipotoxicity in the absence of diabetes. They do not relate to fibrosis, edema, or endoplasmic reticulum stress.


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    No conflict of interest has been declared by the author(s).