Abstract 18444: TRAF5 Deficiency Aggravates Diet-Induced Obesity in Mice
Objective: Accumulation of inflammatory leukocytes is a prerequisite of adipose tissue inflammation during cardiometabolic disease. We recently reported that genetic deficiency of the intracellular signaling adaptor TRAF5 accelerates atherogenesis in mice by increasing inflammatory cell recruitment. Since the latter is instrumental in metabolic disease, we tested the hypothesis that TRAF5 contributes to diet-induced obesity (DIO) in mice.
Methods & Results: To induce metabolic syndrome, wild-type or TRAF5-/- mice consumed a high fat diet (45%kcal) for 20 weeks. TRAF5-/- mice showed an increased weight gain (78,8 ± 1,8% vs. 32,4 ±2,7 % wild-type), impaired insulin tolerance, and increased fasting blood glucose. Weight of liver and peripheral fat pats except epididymal fat were increased in TRAF5-/- mice. Analysis of the peripheral blood revealed leukocytosis driven by a relative increase in B-cells and monocytes. Analysis of inflammatory cells in the stromal vascular fraction revealed an increase in T-cells, Ly6Chigh monocytes, and a decrease of regulatory T-cells compared with respective controls. In accord, invasion of leukocytes into the peritoneal cavity was increased in TRAF5-/- mice while energy expenditure and food intake were not affected as assessed by metabolic caging.
Conclusion: We show that TRAF5 deficiency in mice aggravates diet-induced obesity. A pro-inflammatory blood composition and increased adipose tissue inflammation are the likely mechanisms. Our data indicate that TRAF5 signaling may favorable affect metabolic disease.
Author Disclosures: F. Willecke: None. M.C. Gissler: None. N. Anto Michel: None. C. Härtner: None. I. Hilgendorf: None. P. Stachon: None. D. Wolf: None. A. Zirlik: None.
- © 2016 by American Heart Association, Inc.