Abstract 20367: Interleukin-18 Mediates Left Ventricular Dysfunction Induced by Western Diet Independent of Metabolic Changes in the Mouse
Background: Western diet (WD), rich in saturated fat and sugars, can induce cardiac dysfunction through unknown mechanisms. Saturated fat and sugars can prime and activate the NLRP3 inflammasome that produces the cardiodepressant pro-inflammatory cytokine interleukin-18 (IL-18).
Hypothesis: We hypothesize that IL-18 mediates WD-induced cardiac dysfunction, independent on the effects on glucose metabolism.
Methods: Adult C57BL/6J (WT)(N=7) and IL-18 knock out (KO)(N=9) mice were randomly assigned to either standard mouse diet (SD, saturated fat 0.8%, sucrose 0%) or WD (saturated fat 12.8%, sucrose 30%) for 8 weeks. Transthoracic echocardiography was performed at baseline and at 8 weeks to measure LV fractional shortening (LVFS), isovolumetric relaxation time (IRT) and myocardial performance index (MPI). Food intake was measured daily, body weight weekly, and fasting glycemia at baseline and at 8 weeks.
Results: After 8 weeks, WD-fed WT mice had significantly lower LVFS, higher IRT and MPI than WD-fed IL-18KO mice (Figure 1, panels A, B and C). When fed WD, IL-18KO mice experienced a greater 8-week cumulative caloric intake (804±1.8 vs 765±9.8 kcal; p<0.001) and greater increase in body weight compared to WT mice (Figure 1, panel D) without any significant difference in hyperglycemia levels (data not shown).
Conclusion: IL-18 mediates WD-induced cardiac dysfunction independent of food intake, obesity and hyperglycemia. These data indicate a disconnect between metabolic changes and cardiac dysfunction in obesity, and suggest that IL-18 may represent a targeted therapeutic strategy in obese patients with cardiac dysfunction.
Author Disclosures: S. Carbone: None. P.J. Lee: None. G. Mauro: None. E. Mezzaroma: None. J.A. Regan: None. D. Kraskauskas: None. R. Buzzetti: None. B.W. Van Tassell: None. A. Abbate: None. S. Toldo: None.
- © 2016 by American Heart Association, Inc.