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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / immunology*
  • Adipose Tissue / metabolism
  • Animals
  • Antibodies, Neutralizing / administration & dosage
  • Blood Glucose / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Ligand / deficiency*
  • CD40 Ligand / genetics
  • CD40 Ligand / immunology
  • Disease Models, Animal
  • Fatty Liver / genetics
  • Fatty Liver / immunology
  • Fatty Liver / metabolism
  • Fatty Liver / prevention & control*
  • Inflammation Mediators / metabolism
  • Insulin / blood
  • Insulin Resistance*
  • Lipid Metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / complications
  • Obesity / genetics
  • Obesity / immunology
  • Obesity / metabolism
  • Obesity / physiopathology
  • Obesity / prevention & control*
  • Panniculitis / genetics
  • Panniculitis / immunology
  • Panniculitis / metabolism
  • Panniculitis / prevention & control*
  • Time Factors
  • Weight Gain

Substances

  • Antibodies, Neutralizing
  • Blood Glucose
  • Inflammation Mediators
  • Insulin
  • CD40 Ligand