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Arterioscler Thromb Vasc Biol. 2011 Oct;31(10):2251-60. doi: 10.1161/ATVBAHA.111.231357. Epub 2011 Aug 4.

CD40L deficiency ameliorates adipose tissue inflammation and metabolic manifestations of obesity in mice.

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1
Department of Pathology, Cardiovascular Research Institute Maastricht, Maastricht University, the Netherlands.

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.

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.

PMID:
21817098
DOI:
10.1161/ATVBAHA.111.231357
[Indexed for MEDLINE]
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