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

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

Research output: Contribution to journalArticle

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Abstract

Background and Aims: 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. Methods: 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. Results/Interpretation: 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. Conclusion/Interpretation: We identified adipocyte-inherent metabolic alterations discriminating between MHO and MUHO.

Original languageEnglish
Article numbere93148
JournalPLoS One
Volume9
Issue number4
DOIs
Publication statusPublished - 2 Apr 2014
Externally publishedYes

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adipocytes
Phosphatidylcholines
Adipocytes
Insulin
phosphatidylcholines
Metabolites
Arachidonic Acid
insulin resistance
Aspartic Acid
Fats
aspartic acid
Arachidonic Acids
arachidonic acid
Prostaglandin Antagonists
Spermidine
Docosahexaenoic Acids
Adipose Tissue
Biopsy
Biomarkers
obesity

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals. / Böhm, Anja; Halama, Anna; Meile, Tobias; Zdichavsky, Marty; Lehmann, Rainer; Weigert, Cora; Fritsche, Andreas; Stefan, Norbert; Königsrainer, Alfred; Häring, Hans Ulrich; De Angelis, Martin Hrabě; Adamski, Jerzy; Staiger, Harald.

In: PLoS One, Vol. 9, No. 4, e93148, 02.04.2014.

Research output: Contribution to journalArticle

Böhm, A, Halama, A, Meile, T, Zdichavsky, M, Lehmann, R, Weigert, C, Fritsche, A, Stefan, N, Königsrainer, A, Häring, HU, De Angelis, MH, Adamski, J & Staiger, H 2014, 'Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals', PLoS One, vol. 9, no. 4, e93148. https://doi.org/10.1371/journal.pone.0093148
Böhm, Anja ; Halama, Anna ; Meile, Tobias ; Zdichavsky, Marty ; Lehmann, Rainer ; Weigert, Cora ; Fritsche, Andreas ; Stefan, Norbert ; Königsrainer, Alfred ; Häring, Hans Ulrich ; De Angelis, Martin Hrabě ; Adamski, Jerzy ; Staiger, Harald. / Metabolic signatures of cultured human adipocytes from metabolically healthy versus unhealthy obese individuals. In: PLoS One. 2014 ; Vol. 9, No. 4.
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abstract = "Background and Aims: 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. Methods: 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. Results/Interpretation: 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. Conclusion/Interpretation: We identified adipocyte-inherent metabolic alterations discriminating between MHO and MUHO.",
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AU - Weigert, Cora

AU - Fritsche, Andreas

AU - Stefan, Norbert

AU - Königsrainer, Alfred

AU - Häring, Hans Ulrich

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