Keuper, M. ; Sachs, S. ; Walheim, E. ; Berti, L. ; Raedle, B. ; Tews, D.* ; Fischer-Posovszky, P.* ; Wabitsch, M.* ; Hrabě de Angelis, M. ; Kastenmüller, G. ; Tschöp, M.H. ; Jastroch, M. ; Staiger, H. ; Hofmann, S.M.
Activated macrophages control human adipocyte mitochondrial bioenergetics via secreted factors.
Mol. Metab. 6, 1226-1239 (2017)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Cytokines, Oxidative phosphorylation, Glycolysis, Cellular metabolism; Adipose-tissue Macrophages; Induced Insulin-resistance; Necrosis-factor-alpha; Diet-induced Obesity; Soluble Cd40 Ligand; Gene-expression; Beige Fat; Subcutaneous Adipocytes; Adaptive Thermogenesis; Adiponectin Secretion
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2017
Prepublished im Jahr
HGF-Berichtsjahr
2017
ISSN (print) / ISBN
2212-8778
e-ISSN
2212-8778
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 6,
Heft: 10,
Seiten: 1226-1239
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Elsevier
Verlagsort
Amsterdam
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
90000 - German Center for Diabetes Research
30201 - Metabolic Health
30505 - New Technologies for Biomedical Discoveries
Forschungsfeld(er)
Helmholtz Diabetes Center
Genetics and Epidemiology
Enabling and Novel Technologies
PSP-Element(e)
G-502400-001
G-502200-001
G-501900-065
G-503700-001
G-501900-221
G-502390-001
G-500600-001
Förderungen
Copyright
Erfassungsdatum
2017-07-27