Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands.
Arterioscler Thromb Vasc Biol. 2011 Oct;31(10):2251-60. doi: 10.1161/ATVBAHA.111.231357. Epub 2011 Aug 4.
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.
肥胖脂肪组织表现出慢性炎症的特征，这会促进代谢紊乱的发展。免疫细胞之间相互作用的机制，以及涉及的参与者，仍不清楚。CD40-CD40L 共刺激二聚体在免疫反应和动脉粥样硬化等疾病中起着关键作用，因此可能是肥胖的介质。在这里，我们研究了 CD40L 是否参与脂肪组织炎症及其相关的代谢变化。
为了评估 CD40L 在体内肥胖中的潜在作用，我们评估了 18 周高脂肪喂养对 CD40L(+/+)和 CD40L(-/-)小鼠的代谢和炎症后果。此外，C57Bl6 小鼠在喂食高脂肪饮食的同时注射中和抗 CD40L(αCD40L)抗体 12 周。CD40L 的基因缺失减轻了饮食诱导的肥胖、肝脂肪变性和全身胰岛素敏感性的增加。在脂肪组织中，它损害了肥胖诱导的免疫细胞浸润和相关的葡萄糖和脂质代谢恶化。因此，αCD40L 治疗改善了全身胰岛素敏感性、葡萄糖耐量和脂肪组织中 CD4(+)T 细胞浸润，而对脂肪组织重量的影响有限。
CD40L 在肥胖引起的炎症和代谢并发症的发展中起着至关重要的作用。
