Abstract 485: CD44 Deficiency Protects Against Diet-Induced Obesity and Reduces Adipose Tissue Inflammation in Mice
Natural genetic variation between C57BL/6J AND C3H/HeJ affects susceptibility to atherosclerosis and its related risk factors. Recent studies from our laboratory identified a genetic network of co-expressed genes regulating these traits and our mechanistic studies in macrophages identified CD44 as a critical mediator of the network. We found that perturbation of CD44 dramatically affects the network and has possible pleotropic effects on metabolism. CD44 is associated with altered immune function in mice and has been reported to affect atherosclerosis and diabetes, but the underlying mechanism is unclear. Our current hypothesis that CD44 is a critical mediator of a genetic network altering systemic inflammation associated with metabolic syndrome. Thus, we measured the effects of CD44 deficiency in mice challenged with a high fat diet. Male mice (either C57BL6 wild-type or CD44-/-) were fed a diet high in fat, cholesterol, and sucrose for 7 weeks. While there was no significant difference in final body weight, fat mass accumulation was reduced 30% in CD44-/- mice, relative to wild-type mice. Reduced fat mass could not be attributed to reduced food intake or an increase in energy expenditure as measured by indirect calorimetry. However, we observed altered adipose associated inflammation in epidydimal adipose tissue. We found that expression of macrophage markers F4/80, CD11b, and CD14 were decreased 40-60% and inflammation marker TNF-alpha was reduced 40% in CD44-/- mice, relative to wild-type mice. In conclusion, we demonstrate that mice deficient in CD44 exhibit improved metabolic parameters and adiposity, and this may be related to altered adipose tissue inflammation. We are currently extending these studies to include CD44-/- on a C3H/HeJ genetic background to determine if natural variation in macrophage phenotype modulates CD44’s role in adipose tissue associated inflammation.
Author Disclosures: M.A. VerHague: None. J. Albright: None. B.J. Bennett: None.
- © 2015 by American Heart Association, Inc.