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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-10-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877817304477 |
| _version_ | 1819151283331792896 |
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| author | Michaela Keuper Stephan Sachs Ellen Walheim Lucia Berti Bernhard Raedle Daniel Tews Pamela Fischer-Posovszky Martin Wabitsch Martin Hrabě de Angelis Gabi Kastenmüller Matthias H. Tschöp Martin Jastroch Harald Staiger Susanna M. Hofmann |
| author_facet | Michaela Keuper Stephan Sachs Ellen Walheim Lucia Berti Bernhard Raedle Daniel Tews Pamela Fischer-Posovszky Martin Wabitsch Martin Hrabě de Angelis Gabi Kastenmüller Matthias H. Tschöp Martin Jastroch Harald Staiger Susanna M. Hofmann |
| author_sort | Michaela Keuper |
| collection | DOAJ |
| 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/m2). 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. |
| first_indexed | 2024-12-22T14:30:56Z |
| format | Article |
| id | doaj.art-471836ca196740ea990d3ada27524382 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-22T14:30:56Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-471836ca196740ea990d3ada275243822022-12-21T18:22:45ZengElsevierMolecular Metabolism2212-87782017-10-016101226123910.1016/j.molmet.2017.07.008Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factorsMichaela Keuper0Stephan Sachs1Ellen Walheim2Lucia Berti3Bernhard Raedle4Daniel Tews5Pamela Fischer-Posovszky6Martin Wabitsch7Martin Hrabě de Angelis8Gabi Kastenmüller9Matthias H. Tschöp10Martin Jastroch11Harald Staiger12Susanna M. Hofmann13Institute of Diabetes and Regeneration Research, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, GermanyInstitute of Diabetes and Regeneration Research, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, GermanyGerman Center for Diabetes Research (DZD), Neuherberg, GermanyGerman Center for Diabetes Research (DZD), Neuherberg, GermanyGerman Center for Diabetes Research (DZD), Neuherberg, GermanyDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center, Ulm, GermanyDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center, Ulm, GermanyDivision of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, University Medical Center, Ulm, GermanyGerman Center for Diabetes Research (DZD), Neuherberg, GermanyInstitute of Bioinformatics and Systems Biology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, GermanyGerman Center for Diabetes Research (DZD), Neuherberg, GermanyGerman Center for Diabetes Research (DZD), Neuherberg, GermanyGerman Center for Diabetes Research (DZD), Neuherberg, GermanyInstitute of Diabetes and Regeneration Research, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg, GermanyObjective: 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/m2). 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.http://www.sciencedirect.com/science/article/pii/S2212877817304477CytokinesOxidative phosphorylationGlycolysisCellular metabolism |
| spellingShingle | Michaela Keuper Stephan Sachs Ellen Walheim Lucia Berti Bernhard Raedle Daniel Tews Pamela Fischer-Posovszky Martin Wabitsch Martin Hrabě de Angelis Gabi Kastenmüller Matthias H. Tschöp Martin Jastroch Harald Staiger Susanna M. Hofmann Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors Molecular Metabolism Cytokines Oxidative phosphorylation Glycolysis Cellular metabolism |
| 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 | Cytokines Oxidative phosphorylation Glycolysis Cellular metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2212877817304477 |
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