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
Y1 - 2011
N2 - 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. 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. CD40L plays a crucial role in the development of obesity-induced inflammation and metabolic complications
AB - 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. 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. CD40L plays a crucial role in the development of obesity-induced inflammation and metabolic complications
U2 - https://doi.org/10.1161/ATVBAHA.111.231357
DO - https://doi.org/10.1161/ATVBAHA.111.231357
M3 - Article
C2 - 21817098
SN - 1079-5642
VL - 31
SP - 2251
EP - 2260
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
IS - 10
ER -