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Böhm, A. ; Keuper, M. ; Meile, T.* ; Zdichavsky, M.* ; Fritsche, A. ; Häring, H.-U. ; Hrabě de Angelis, M. ; Staiger, H. ; Frankó, A.

Increased mitochondrial respiration of adipocytes from metabolically unhealthy obese compared to healthy obese individuals.

Sci. Rep. 10:12407 (2020)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Beta-cell Dysfunction; Key Protective Factor; Insulin-resistance; Adipose-tissue; Oxygen-consumption; Arachidonic-acid; Fat; Sensitivity; Lipolysis; Stimulation
Language english
Publication Year 2020
HGF-reported in Year 2020
ISSN (print) / ISBN 2045-2322
e-ISSN 2045-2322
Journal Scientific Reports
Quellenangaben Volume: 10, Issue: 1, Pages: , Article Number: 12407 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research and Metabolic Diseases (IDM)
Institute of Experimental Genetics (IEG)
POF-Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
Research field(s) Helmholtz Diabetes Center
Genetics and Epidemiology
PSP Element(s) G-502400-001
G-500600-001
DOI 10.1038/s41598-020-69016-9
WOS ID WOS:000555459900001
Scopus ID 85088513245
PubMed ID 32709986
Erfassungsdatum 2020-07-30
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