Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.

<h4>Background and aims</h4>Among obese subjects, metabolically healthy and unhealthy obesity (MHO/MUHO) can be differentiated: the latter is characterized by whole-body insulin resistance, hepatic steatosis, and subclinical inflammation. Aim of this study was, to identify adipocyte-spec...

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Autores principales:	Anja Böhm, Anna Halama, Tobias Meile, Marty Zdichavsky, Rainer Lehmann, Cora Weigert, Andreas Fritsche, Norbert Stefan, Alfred Königsrainer, Hans-Ulrich Häring, Martin Hrabě de Angelis, Jerzy Adamski, Harald Staiger
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b1a766f66e7b461b9e6ca51131604475
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spelling	oai:doaj.org-article:b1a766f66e7b461b9e6ca511316044752021-11-18T08:25:19ZMetabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.1932-620310.1371/journal.pone.0093148https://doaj.org/article/b1a766f66e7b461b9e6ca511316044752014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24695116/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background and aims</h4>Among obese subjects, metabolically healthy and unhealthy obesity (MHO/MUHO) can be differentiated: the latter is characterized by whole-body insulin resistance, hepatic steatosis, and subclinical inflammation. Aim of this study was, to identify adipocyte-specific metabolic signatures and functional biomarkers for MHO versus MUHO.<h4>Methods</h4>10 insulin-resistant (IR) vs. 10 insulin-sensitive (IS) non-diabetic morbidly obese (BMI >40 kg/m2) Caucasians were matched for gender, age, BMI, and percentage of body fat. From subcutaneous fat biopsies, primary preadipocytes were isolated and differentiated to adipocytes in vitro. About 280 metabolites were investigated by a targeted metabolomic approach intracellularly, extracellularly, and in plasma.<h4>Results/interpretation</h4>Among others, aspartate was reduced intracellularly to one third (p = 0.0039) in IR adipocytes, pointing to a relative depletion of citric acid cycle metabolites or reduced aspartate uptake in MUHO. Other amino acids, already known to correlate with diabetes and/or obesity, were identified to differ between MUHO's and MHO's adipocytes, namely glutamine, histidine, and spermidine. Most species of phosphatidylcholines (PCs) were lower in MUHO's extracellular milieu, though simultaneously elevated intracellularly, e.g., PC aa C32∶3, pointing to increased PC synthesis and/or reduced PC release. Furthermore, altered arachidonic acid (AA) metabolism was found: 15(S)-HETE (15-hydroxy-eicosatetraenoic acid; 0 vs. 120pM; p = 0.0014), AA (1.5-fold; p = 0.0055) and docosahexaenoic acid (DHA, C22∶6; 2-fold; p = 0.0033) were higher in MUHO. This emphasizes a direct contribution of adipocytes to local adipose tissue inflammation. Elevated DHA, as an inhibitor of prostaglandin synthesis, might be a hint for counter-regulatory mechanisms in MUHO.<h4>Conclusion/interpretation</h4>We identified adipocyte-inherent metabolic alterations discriminating between MHO and MUHO.Anja BöhmAnna HalamaTobias MeileMarty ZdichavskyRainer LehmannCora WeigertAndreas FritscheNorbert StefanAlfred KönigsrainerHans-Ulrich HäringMartin Hrabě de AngelisJerzy AdamskiHarald StaigerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 4, p e93148 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anja Böhm Anna Halama Tobias Meile Marty Zdichavsky Rainer Lehmann Cora Weigert Andreas Fritsche Norbert Stefan Alfred Königsrainer Hans-Ulrich Häring Martin Hrabě de Angelis Jerzy Adamski Harald Staiger Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.
description	<h4>Background and aims</h4>Among obese subjects, metabolically healthy and unhealthy obesity (MHO/MUHO) can be differentiated: the latter is characterized by whole-body insulin resistance, hepatic steatosis, and subclinical inflammation. Aim of this study was, to identify adipocyte-specific metabolic signatures and functional biomarkers for MHO versus MUHO.<h4>Methods</h4>10 insulin-resistant (IR) vs. 10 insulin-sensitive (IS) non-diabetic morbidly obese (BMI >40 kg/m2) Caucasians were matched for gender, age, BMI, and percentage of body fat. From subcutaneous fat biopsies, primary preadipocytes were isolated and differentiated to adipocytes in vitro. About 280 metabolites were investigated by a targeted metabolomic approach intracellularly, extracellularly, and in plasma.<h4>Results/interpretation</h4>Among others, aspartate was reduced intracellularly to one third (p = 0.0039) in IR adipocytes, pointing to a relative depletion of citric acid cycle metabolites or reduced aspartate uptake in MUHO. Other amino acids, already known to correlate with diabetes and/or obesity, were identified to differ between MUHO's and MHO's adipocytes, namely glutamine, histidine, and spermidine. Most species of phosphatidylcholines (PCs) were lower in MUHO's extracellular milieu, though simultaneously elevated intracellularly, e.g., PC aa C32∶3, pointing to increased PC synthesis and/or reduced PC release. Furthermore, altered arachidonic acid (AA) metabolism was found: 15(S)-HETE (15-hydroxy-eicosatetraenoic acid; 0 vs. 120pM; p = 0.0014), AA (1.5-fold; p = 0.0055) and docosahexaenoic acid (DHA, C22∶6; 2-fold; p = 0.0033) were higher in MUHO. This emphasizes a direct contribution of adipocytes to local adipose tissue inflammation. Elevated DHA, as an inhibitor of prostaglandin synthesis, might be a hint for counter-regulatory mechanisms in MUHO.<h4>Conclusion/interpretation</h4>We identified adipocyte-inherent metabolic alterations discriminating between MHO and MUHO.
format	article
author	Anja Böhm Anna Halama Tobias Meile Marty Zdichavsky Rainer Lehmann Cora Weigert Andreas Fritsche Norbert Stefan Alfred Königsrainer Hans-Ulrich Häring Martin Hrabě de Angelis Jerzy Adamski Harald Staiger
author_facet	Anja Böhm Anna Halama Tobias Meile Marty Zdichavsky Rainer Lehmann Cora Weigert Andreas Fritsche Norbert Stefan Alfred Königsrainer Hans-Ulrich Häring Martin Hrabě de Angelis Jerzy Adamski Harald Staiger
author_sort	Anja Böhm
title	Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.
title_short	Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.
title_full	Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.
title_fullStr	Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.
title_full_unstemmed	Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.
title_sort	metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/b1a766f66e7b461b9e6ca51131604475
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Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals.

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