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. CONCLUSIONS: CD40L plays a crucial role in the development of obesity-induced inflammation and metabolic complications.
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. CONCLUSIONS:CD40L plays a crucial role in the development of obesity-induced inflammation and metabolic complications.
Authors: S M van den Berg; T T P Seijkens; P J H Kusters; B Zarzycka; L Beckers; M den Toom; M J J Gijbels; A Chatzigeorgiou; C Weber; M P J de Winther; T Chavakis; G A F Nicolaes; E Lutgens Journal: Int J Obes (Lond) Date: 2014-11-13 Impact factor: 5.095
Authors: David L Morris; Kelsie E Oatmen; Taleen A Mergian; Kae Won Cho; Jennifer L DelProposto; Kanakadurga Singer; Carmella Evans-Molina; Robert W O'Rourke; Carey N Lumeng Journal: J Leukoc Biol Date: 2015-12-11 Impact factor: 4.962
Authors: Chang-An Guo; Sophia Kogan; Shinya U Amano; Mengxi Wang; Sezin Dagdeviren; Randall H Friedline; Myriam Aouadi; Jason K Kim; Michael P Czech Journal: Am J Physiol Endocrinol Metab Date: 2013-03-12 Impact factor: 4.310