Abstract 15272: Genetic Deficiency of CD40L Attenuates Diet-Induced Adipose Tissue Inflammation - but Does Not Protect From Insulin Resistance and Hepatic Steatosis in Mice
Background: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L - an established marker and mediator of cardiovascular disease - induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo.
Methods and Results: WT or CD40L-/- mice consumed a high fat diet (HFD) for 20 weeks (n>15 per group). Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L-/- mice. Accordingly, CD40L deficiency partially protected from weight gain and fat deposition in the early stages of diet-induced obesity (DIO). Also, circulating low-density lipoproteins and insulin levels were lower in CD40L-/- mice. However, CD40L-/- mice consuming HFD were not protected from the onset of insulin resistance and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L-/- mice consuming a low fat diet (LFD) showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels.
Conclusion: We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and the metabolic disease.
- © 2011 by American Heart Association, Inc.