| Autor: |
Böhm A; Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, University Hospital Tübingen, Eberhard Karls University Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany. anja.moller@med.uni-tuebingen.de.; German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung, DZD), Neuherberg, Germany. anja.moller@med.uni-tuebingen.de.; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich At the Eberhard Karls University Tübingen, Tübingen, Germany. anja.moller@med.uni-tuebingen.de., Keuper M; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich At the Eberhard Karls University Tübingen, Tübingen, Germany.; Department of Molecular Bioscience, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden., Meile T; Clinic for General, Visceral, Thoracic and Transplant Surgery, Klinikum Stuttgart, Bad Cannstatt, Germany., Zdichavsky M; Department of General, Visceral and Transplant Surgery, University Hospital, Eberhard Karls University Tübingen, Tübingen, Germany., Fritsche A; Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, University Hospital Tübingen, Eberhard Karls University Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.; German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung, DZD), Neuherberg, Germany.; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich At the Eberhard Karls University Tübingen, Tübingen, Germany., Häring HU; Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, University Hospital Tübingen, Eberhard Karls University Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.; German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung, DZD), Neuherberg, Germany.; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich At the Eberhard Karls University Tübingen, Tübingen, Germany.; Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany., de Angelis MH; German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung, DZD), Neuherberg, Germany.; Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.; Chair of Experimental Genetics, Technical University München, Freising-Weihenstephan, Germany., Staiger H; German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung, DZD), Neuherberg, Germany.; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich At the Eberhard Karls University Tübingen, Tübingen, Germany.; Interfaculty Centre for Pharmacogenomics and Pharma Research at the Eberhard Karls University Tübingen, Tübingen, Germany.; Institute of Pharmaceutical Sciences, Department of Pharmacy and Biochemistry, Eberhard Karls University Tübingen, Tübingen, Germany., Franko A; Department of Internal Medicine IV, Division of Endocrinology, Diabetology, Nephrology, University Hospital Tübingen, Eberhard Karls University Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany.; German Center for Diabetes Research (Deutsches Zentrum für Diabetesforschung, DZD), Neuherberg, Germany.; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich At the Eberhard Karls University Tübingen, Tübingen, Germany. |
| Abstrakt: |
Among obese subjects, metabolically healthy (MHO) and unhealthy obese (MUHO) subjects exist, the latter being characterized by whole-body insulin resistance, hepatic steatosis, and subclinical inflammation. Insulin resistance and obesity are known to associate with alterations in mitochondrial density, morphology, and function. Therefore, we assessed mitochondrial function in human subcutaneous preadipocytes as well as in differentiated adipocytes derived from well-matched donors. Primary subcutaneous preadipocytes from 4 insulin-resistant (MUHO) versus 4 insulin-sensitive (MHO), non-diabetic, morbidly obese Caucasians (BMI > 40 kg/m 2 ), matched for sex, age, BMI, and percentage of body fat, were differentiated in vitro to adipocytes. Real-time cellular respiration was measured using an XF24 Extracellular Flux Analyzer (Seahorse). Lipolysis was stimulated by forskolin (FSK) treatment. Mitochondrial respiration was fourfold higher in adipocytes versus preadipocytes (p = 1.6*10 -9 ). In adipocytes, a negative correlation of mitochondrial respiration with donors' insulin sensitivity was shown (p = 0.0008). Correspondingly, in adipocytes of MUHO subjects, an increased basal respiration (p = 0.002), higher proton leak (p = 0.04), elevated ATP production (p = 0.01), increased maximal respiration (p = 0.02), and higher spare respiratory capacity (p = 0.03) were found, compared to MHO. After stimulation with FSK, the differences in ATP production, maximal respiration and spare respiratory capacity were blunted. The differences in mitochondrial respiration between MUHO/MHO were not due to altered mitochondrial content, fuel switch, or lipid metabolism. Thus, despite the insulin resistance of MUHO, we could clearly show an elevated mitochondrial respiration of MUHO adipocytes. We suggest that the higher mitochondrial respiration reflects a compensatory mechanism to cope with insulin resistance and its consequences. Preserving this state of compensation might be an attractive goal for preventing or delaying the transition from insulin resistance to overt diabetes. |
