title: The complement anaphylatoxin C5a receptor contributes to obese adipose tissue inflammation and insulin resistance.
abstract: Obese adipose tissue (AT) inflammation contributes critically to development of insulin resistance. The complement anaphylatoxin C5a receptor (C5aR) has been implicated in inflammatory processes and as regulator of macrophage activation and polarization. However, the role of C5aR in obesity and AT inflammation has not been addressed. We engaged the model of diet-induced obesity and found that expression of C5aR was significantly upregulated in the obese AT, compared with lean AT. In addition, C5a was present in obese AT in the proximity of macrophage-rich crownlike structures. C5aR-sufficient and -deficient mice were fed a high-fat diet (HFD) or a normal diet (ND). C5aR deficiency was associated with increased AT weight upon ND feeding in males, but not in females, and with increased adipocyte size upon ND and HFD conditions in males. However, obese C5aR(-/-) mice displayed improved systemic and AT insulin sensitivity. Improved AT insulin sensitivity in C5aR(-/-) mice was associated with reduced accumulation of total and proinflammatory M1 macrophages in the obese AT, increased expression of IL-10, and decreased AT fibrosis. In contrast, no difference in β cell mass was observed owing to C5aR deficiency under an HFD. These results suggest that C5aR contributes to macrophage accumulation and M1 polarization in the obese AT and thereby to AT dysfunction and development of AT insulin resistance.
authors.affiliation: Division of Vascular Inflammation, Diabetes and Kidney, Department of Medicine III, Dresden University, 01307 Dresden, Germany;
authors.forename: Julia
authors.initials: J
authors.lastname: Phieler
authors.forename: Kyoung-Jin
authors.initials: KJ
authors.lastname: Chung
authors.forename: Antonios
authors.initials: A
authors.lastname: Chatzigeorgiou
authors.forename: Anne
authors.initials: A
authors.lastname: Klotzsche-von Ameln
authors.forename: Ruben
authors.initials: R
authors.lastname: Garcia-Martin
authors.forename: David
authors.initials: D
authors.lastname: Sprott
authors.forename: Maria
authors.initials: M
authors.lastname: Moisidou
authors.forename: Theodora
authors.initials: T
authors.lastname: Tzanavari
authors.forename: Barbara
authors.initials: B
authors.lastname: Ludwig
authors.forename: Elena
authors.initials: E
authors.lastname: Baraban
authors.forename: Monika
authors.initials: M
authors.lastname: Ehrhart-Bornstein
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: Hassan
authors.initials: H
authors.lastname: Mziaut
authors.forename: Michele
authors.initials: M
authors.lastname: Solimena
authors.forename: Katia P
authors.initials: KP
authors.lastname: Karalis
authors.forename: Matina
authors.initials: M
authors.lastname: Economopoulou
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.forename: Triantafyllos
authors.initials: T
authors.lastname: Chavakis
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000378:metabolism; D000273:Adipose Tissue / Q000276:immunology* / Q000378:metabolism*; D000818:Animals; D015936:Complement C5a / Q000378:metabolism; D004041:Dietary Fats / Q000276:immunology / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007333:Insulin Resistance / Q000276:immunology*; D050417:Insulin-Secreting Cells / Q000378:metabolism; D016753:Interleukin-10 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000276:immunology / Q000378:metabolism; D044087:Receptor, Anaphylatoxin C5a / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004041:Dietary Fats; D044087:Receptor, Anaphylatoxin C5a; D016753:Interleukin-10; D015936:Complement C5a
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