Cargando…

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

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 densi...

Descripción completa

Detalles Bibliográficos
Autores principales: Böhm, Anja, Keuper, Michaela, Meile, Tobias, Zdichavsky, Marty, Fritsche, Andreas, Häring, Hans-Ulrich, de Angelis, Martin Hrabě, Staiger, Harald, Franko, Andras
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382448/
https://www.ncbi.nlm.nih.gov/pubmed/32709986
http://dx.doi.org/10.1038/s41598-020-69016-9
_version_ 1783563242947215360
author Böhm, Anja
Keuper, Michaela
Meile, Tobias
Zdichavsky, Marty
Fritsche, Andreas
Häring, Hans-Ulrich
de Angelis, Martin Hrabě
Staiger, Harald
Franko, Andras
author_facet Böhm, Anja
Keuper, Michaela
Meile, Tobias
Zdichavsky, Marty
Fritsche, Andreas
Häring, Hans-Ulrich
de Angelis, Martin Hrabě
Staiger, Harald
Franko, Andras
author_sort Böhm, Anja
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7382448
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-73824482020-07-28 Increased mitochondrial respiration of adipocytes from metabolically unhealthy obese compared to healthy obese individuals Böhm, Anja Keuper, Michaela Meile, Tobias Zdichavsky, Marty Fritsche, Andreas Häring, Hans-Ulrich de Angelis, Martin Hrabě Staiger, Harald Franko, Andras Sci Rep Article 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. Nature Publishing Group UK 2020-07-24 /pmc/articles/PMC7382448/ /pubmed/32709986 http://dx.doi.org/10.1038/s41598-020-69016-9 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Böhm, Anja
Keuper, Michaela
Meile, Tobias
Zdichavsky, Marty
Fritsche, Andreas
Häring, Hans-Ulrich
de Angelis, Martin Hrabě
Staiger, Harald
Franko, Andras
Increased mitochondrial respiration of adipocytes from metabolically unhealthy obese compared to healthy obese individuals
title Increased mitochondrial respiration of adipocytes from metabolically unhealthy obese compared to healthy obese individuals
title_full Increased mitochondrial respiration of adipocytes from metabolically unhealthy obese compared to healthy obese individuals
title_fullStr Increased mitochondrial respiration of adipocytes from metabolically unhealthy obese compared to healthy obese individuals
title_full_unstemmed Increased mitochondrial respiration of adipocytes from metabolically unhealthy obese compared to healthy obese individuals
title_short Increased mitochondrial respiration of adipocytes from metabolically unhealthy obese compared to healthy obese individuals
title_sort increased mitochondrial respiration of adipocytes from metabolically unhealthy obese compared to healthy obese individuals
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382448/
https://www.ncbi.nlm.nih.gov/pubmed/32709986
http://dx.doi.org/10.1038/s41598-020-69016-9
work_keys_str_mv AT bohmanja increasedmitochondrialrespirationofadipocytesfrommetabolicallyunhealthyobesecomparedtohealthyobeseindividuals
AT keupermichaela increasedmitochondrialrespirationofadipocytesfrommetabolicallyunhealthyobesecomparedtohealthyobeseindividuals
AT meiletobias increasedmitochondrialrespirationofadipocytesfrommetabolicallyunhealthyobesecomparedtohealthyobeseindividuals
AT zdichavskymarty increasedmitochondrialrespirationofadipocytesfrommetabolicallyunhealthyobesecomparedtohealthyobeseindividuals
AT fritscheandreas increasedmitochondrialrespirationofadipocytesfrommetabolicallyunhealthyobesecomparedtohealthyobeseindividuals
AT haringhansulrich increasedmitochondrialrespirationofadipocytesfrommetabolicallyunhealthyobesecomparedtohealthyobeseindividuals
AT deangelismartinhrabe increasedmitochondrialrespirationofadipocytesfrommetabolicallyunhealthyobesecomparedtohealthyobeseindividuals
AT staigerharald increasedmitochondrialrespirationofadipocytesfrommetabolicallyunhealthyobesecomparedtohealthyobeseindividuals
AT frankoandras increasedmitochondrialrespirationofadipocytesfrommetabolicallyunhealthyobesecomparedtohealthyobeseindividuals