title: CD40L deficiency ameliorates adipose tissue inflammation and metabolic manifestations of obesity in mice.
abstract: OBJECTIVE
  Obese adipose tissue shows hallmarks of chronic inflammation, which promotes the development of metabolic disorders. The mechanisms by which immune cells interact with each other or with metabolism-associated cell types, and the players involved, are still unclear. The CD40-CD40L costimulatory dyad plays a pivotal role in immune responses and in diseases such as atherosclerosis and may therefore be a mediator of obesity. Here we investigated whether CD40L is involved in adipose tissue inflammation and its associated metabolic changes.
  
  
  RESULTS
  To assess a putative role of CD40L in obesity in vivo, we evaluated metabolic and inflammatory consequences of 18 weeks of high-fat feeding in CD40L(+/+) and CD40L(-/-) mice. In addition, C57Bl6 mice were injected with neutralizing anti-CD40L (αCD40L) antibody for 12 weeks while being fed a high-fat diet. Genetic deficiency of CD40L attenuated the development of diet-induced obesity, hepatic steatosis, and increased systemic insulin sensitivity. In adipose tissue, it impaired obesity-induced immune cell infiltration and the associated deterioration of glucose and lipid metabolism. Accordingly, αCD40L treatment improved systemic insulin sensitivity, glucose tolerance, and CD4(+) T-cell infiltration in adipose tissue with limited effects on adipose tissue weight.
  
  
  CONCLUSIONS
  CD40L plays a crucial role in the development of obesity-induced inflammation and metabolic complications.
authors.affiliation: Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Poggi
authors.forename: David
authors.initials: D
authors.lastname: Engel
authors.forename: Anette
authors.initials: A
authors.lastname: Christ
authors.forename: Linda
authors.initials: L
authors.lastname: Beckers
authors.forename: Erwin
authors.initials: E
authors.lastname: Wijnands
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Ann
authors.initials: A
authors.lastname: Driessen
authors.forename: Jack
authors.initials: J
authors.lastname: Cleutjens
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
authors.forename: Norbert
authors.initials: N
authors.lastname: Gerdes
authors.forename: Esther
authors.initials: E
authors.lastname: Lutgens
mesh_terms: D000273:Adipose Tissue / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D001786:Blood Glucose / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D023201:CD40 Ligand / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015434:Panniculitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D013997:Time Factors; D015430:Weight Gain
chemical_list: D057134:Antibodies, Neutralizing; D001786:Blood Glucose; D018836:Inflammation Mediators; D007328:Insulin; D023201:CD40 Ligand