title: CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.
abstract: BACKGROUND
  Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo.
  
  
  RESULTS
  WT or CD40L(-/-) mice consumed a high fat diet (HFD) for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/-) mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L(-/-) mice. However, CD40L(-/-) mice consuming HFD were not protected from the onset of diet-induced obesity (DIO), insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/-) mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels.
  
  
  CONCLUSIONS
  We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease.
authors.affiliation: Atherogenesis Research Group, Department of Cardiology, University of Freiburg, Freiburg, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Wolf
authors.forename: Felix
authors.initials: F
authors.lastname: Jehle
authors.forename: Alexandra
authors.initials: A
authors.lastname: Ortiz Rodriguez
authors.forename: Bianca
authors.initials: B
authors.lastname: Dufner
authors.forename: Natalie
authors.initials: N
authors.lastname: Hoppe
authors.forename: Christian
authors.initials: C
authors.lastname: Colberg
authors.forename: Andrey
authors.initials: A
authors.lastname: Lozhkin
authors.forename: Nicole
authors.initials: N
authors.lastname: Bassler
authors.forename: Benjamin
authors.initials: B
authors.lastname: Rupprecht
authors.forename: Ansgar
authors.initials: A
authors.lastname: Wiedemann
authors.forename: Ingo
authors.initials: I
authors.lastname: Hilgendorf
authors.forename: Peter
authors.initials: P
authors.lastname: Stachon
authors.forename: Florian
authors.initials: F
authors.lastname: Willecke
authors.forename: Mark
authors.initials: M
authors.lastname: Febbraio
authors.forename: Constantin
authors.initials: C
authors.lastname: von zur Muhlen
authors.forename: Christoph J
authors.initials: CJ
authors.lastname: Binder
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Andreas
authors.initials: A
authors.lastname: Zirlik
authors.forename: Karlheinz
authors.initials: K
authors.lastname: Peter
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D023201:CD40 Ligand / Q000172:deficiency* / Q000276:immunology*; D018925:Chemokines / Q000235:genetics; D004032:Diet / Q000009:adverse effects*; D004734:Energy Metabolism / Q000235:genetics; D005234:Fatty Liver / Q000235:genetics; D005786:Gene Expression Regulation; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007333:Insulin Resistance / Q000235:genetics; D050356:Lipid Metabolism; D008055:Lipids / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology; D010084:Oxidation-Reduction; D015434:Panniculitis / Q000209:etiology* / Q000235:genetics / Q000276:immunology
chemical_list: D001323:Autoantibodies; D018925:Chemokines; D007074:Immunoglobulin G; D008055:Lipids; D023201:CD40 Ligand