TY - JOUR
T1 - CD40L deficiency ameliorates adipose tissue inflammation and metabolic manifestations of obesity in mice
AU - Poggi, Marjorie
AU - Engel, David
AU - Christ, Anette
AU - Beckers, Linda
AU - Wijnands, Erwin
AU - Boon, Louis
AU - Driessen, Ann
AU - Cleutjens, Jack
AU - Weber, Christian
AU - Gerdes, Norbert
AU - Lutgens, Esther
PY - 2011/10
Y1 - 2011/10
N2 - 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. METHODS AND 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. CONCLUSION-: CD40L plays a crucial role in the development of obesity-induced inflammation and metabolic complications.
AB - 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. METHODS AND 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. CONCLUSION-: CD40L plays a crucial role in the development of obesity-induced inflammation and metabolic complications.
KW - immune system
KW - insulin resistance
KW - leukocytes
KW - metabolism
KW - obesity
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U2 - 10.1161/ATVBAHA.111.231357
DO - 10.1161/ATVBAHA.111.231357
M3 - Article
C2 - 21817098
AN - SCOPUS:80052971178
SN - 1079-5642
VL - 31
SP - 2251
EP - 2260
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 10
ER -