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Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors
OBJECTIVE: Obesity-associated WAT inflammation is characterized by the accumulation and local activation of macrophages (MΦs), and recent data from mouse studies suggest that macrophages are modifiers of adipocyte energy metabolism and mitochondrial function. As mitochondrial dysfunction has been as...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641636/ https://www.ncbi.nlm.nih.gov/pubmed/29031722 http://dx.doi.org/10.1016/j.molmet.2017.07.008 |
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author | Keuper, Michaela Sachs, Stephan Walheim, Ellen Berti, Lucia Raedle, Bernhard Tews, Daniel Fischer-Posovszky, Pamela Wabitsch, Martin Hrabě de Angelis, Martin Kastenmüller, Gabi Tschöp, Matthias H. Jastroch, Martin Staiger, Harald Hofmann, Susanna M. |
author_facet | Keuper, Michaela Sachs, Stephan Walheim, Ellen Berti, Lucia Raedle, Bernhard Tews, Daniel Fischer-Posovszky, Pamela Wabitsch, Martin Hrabě de Angelis, Martin Kastenmüller, Gabi Tschöp, Matthias H. Jastroch, Martin Staiger, Harald Hofmann, Susanna M. |
author_sort | Keuper, Michaela |
collection | PubMed |
description | OBJECTIVE: Obesity-associated WAT inflammation is characterized by the accumulation and local activation of macrophages (MΦs), and recent data from mouse studies suggest that macrophages are modifiers of adipocyte energy metabolism and mitochondrial function. As mitochondrial dysfunction has been associated with obesity and the metabolic syndrome in humans, herein we aimed to delineate how human macrophages may affect energy metabolism of white adipocytes. METHODS: Human adipose tissue gene expression analysis for markers of macrophage activation and tissue inflammation (CD11c, CD40, CD163, CD206, CD80, MCP1, TNFα) in relationship to mitochondrial complex I (NDUFB8) and complex III (UQCRC2) was performed on subcutaneous WAT of 24 women (BMI 20–61 kg/m(2)). Guided by these results, the impact of secreted factors of LPS/IFNγ- and IL10/TGFβ-activated human macrophages (THP1, primary blood-derived) on mitochondrial function in human subcutaneous white adipocytes (SGBS, primary) was determined by extracellular flux analysis (Seahorse technology) and gene/protein expression. RESULTS: Stepwise regression analysis of human WAT gene expression data revealed that a linear combination of CD40 and CD163 was the strongest predictor for mitochondrial complex I (NDUFB8) and complex III (UQCRC2) levels, independent of BMI. IL10/TGFβ-activated MΦs displayed high CD163 and low CD40 expression and secreted factors that decreased UQCRC2 gene/protein expression and ATP-linked respiration in human white adipocytes. In contrast, LPS/IFNγ-activated MΦs showed high CD40 and low CD163 expression and secreted factors that enhanced adipocyte mitochondrial activity resulting in a total difference of 37% in ATP-linked respiration of white adipocytes (p = 0.0024) when comparing the effect of LPS/IFNγ- vs IL10/TGFβ-activated MΦs. CONCLUSION: Our data demonstrate that macrophages modulate human adipocyte energy metabolism via an activation-dependent paracrine mechanism. |
format | Online Article Text |
id | pubmed-5641636 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-56416362017-10-23 Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors Keuper, Michaela Sachs, Stephan Walheim, Ellen Berti, Lucia Raedle, Bernhard Tews, Daniel Fischer-Posovszky, Pamela Wabitsch, Martin Hrabě de Angelis, Martin Kastenmüller, Gabi Tschöp, Matthias H. Jastroch, Martin Staiger, Harald Hofmann, Susanna M. Mol Metab Original Article OBJECTIVE: Obesity-associated WAT inflammation is characterized by the accumulation and local activation of macrophages (MΦs), and recent data from mouse studies suggest that macrophages are modifiers of adipocyte energy metabolism and mitochondrial function. As mitochondrial dysfunction has been associated with obesity and the metabolic syndrome in humans, herein we aimed to delineate how human macrophages may affect energy metabolism of white adipocytes. METHODS: Human adipose tissue gene expression analysis for markers of macrophage activation and tissue inflammation (CD11c, CD40, CD163, CD206, CD80, MCP1, TNFα) in relationship to mitochondrial complex I (NDUFB8) and complex III (UQCRC2) was performed on subcutaneous WAT of 24 women (BMI 20–61 kg/m(2)). Guided by these results, the impact of secreted factors of LPS/IFNγ- and IL10/TGFβ-activated human macrophages (THP1, primary blood-derived) on mitochondrial function in human subcutaneous white adipocytes (SGBS, primary) was determined by extracellular flux analysis (Seahorse technology) and gene/protein expression. RESULTS: Stepwise regression analysis of human WAT gene expression data revealed that a linear combination of CD40 and CD163 was the strongest predictor for mitochondrial complex I (NDUFB8) and complex III (UQCRC2) levels, independent of BMI. IL10/TGFβ-activated MΦs displayed high CD163 and low CD40 expression and secreted factors that decreased UQCRC2 gene/protein expression and ATP-linked respiration in human white adipocytes. In contrast, LPS/IFNγ-activated MΦs showed high CD40 and low CD163 expression and secreted factors that enhanced adipocyte mitochondrial activity resulting in a total difference of 37% in ATP-linked respiration of white adipocytes (p = 0.0024) when comparing the effect of LPS/IFNγ- vs IL10/TGFβ-activated MΦs. CONCLUSION: Our data demonstrate that macrophages modulate human adipocyte energy metabolism via an activation-dependent paracrine mechanism. Elsevier 2017-07-19 /pmc/articles/PMC5641636/ /pubmed/29031722 http://dx.doi.org/10.1016/j.molmet.2017.07.008 Text en © 2017 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original Article Keuper, Michaela Sachs, Stephan Walheim, Ellen Berti, Lucia Raedle, Bernhard Tews, Daniel Fischer-Posovszky, Pamela Wabitsch, Martin Hrabě de Angelis, Martin Kastenmüller, Gabi Tschöp, Matthias H. Jastroch, Martin Staiger, Harald Hofmann, Susanna M. Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors |
title | Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors |
title_full | Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors |
title_fullStr | Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors |
title_full_unstemmed | Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors |
title_short | Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors |
title_sort | activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5641636/ https://www.ncbi.nlm.nih.gov/pubmed/29031722 http://dx.doi.org/10.1016/j.molmet.2017.07.008 |
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