Abstract 20195: NLRP3 Inflammasome Inhibitor Prevents Cardiac Dysfunction Induced by Western Diet in the Mouse
Introduction: A diet rich in saturated fat and sugars, Western diet (WD), is sufficient to induce cardiac dysfunction in the mouse. Saturated fats and sugars can prime and activate the NLRP3 inflammasome producing cardiodepressant pro-inflammatory cytokines.
Hypothesis: We hypothesized that administration of an NLRP3 inflammasome inhibitor (NLRP3inh) would prevent WD-induced cardiac dysfunction.
Methods: Eight week-old CD1 male mice were randomly assigned to either WD (saturated fat 12.8%, sucrose 30%) with (N=10) or without (N=8) 0.15% NLRP3inh 16673-34-0, or Standard Diet (SD)(saturated fat 0.8%, sucrose 0%) with (N=8) or without (N=7) NLRP3inh for 12 weeks. Oral glucose tolerance test (2 g/kg) was performed at baseline and at 12 weeks. Food intake was measured daily and body weight weekly. Transthoracic echocardiography at baseline and 12 weeks was performed to measure interval changes in LV fractional shortening (LVFS), isovolumetric relaxation time (IRT) and myocardial performance index (MPI).
Results: When compared with SD-fed mice, WD-fed mice had higher daily caloric intake (21±0.5 vs 17±0.9 kcal; p<0.001), increased body weight (Figure 1A) and worse glucose 2 hours after oral load (173±14 vs 125±13 mg/dL; p=0.03). WD induced diastolic dysfunction, as shown by increases in IRT and MPI (Figure 1B and 1C), without changes in LVFS. The NLRP3inh prevented cardiac diastolic dysfunction in WD mice, as shown by preservation of IRT and MPI (Figure panel B and C). Body weight (Figure 1A) and glucose tolerance were not improved by treatment by NLRP3 inhibitor (data not shown).
Conclusions: The data show, for the first time, that cardiac diastolic dysfunction induced by WD is prevented in mice treated with NLRP3inh in the diet, independent of the effects on body weight or glucose metabolism, suggesting a key role of the NLRP3 inflammasome in the pathogenesis of diet-induced diastolic dysfunction. Further studies in patients with diastolic dysfunction are warranted.
Author Disclosures: S. Carbone: None. G. Mauro: None. E. Mezzaroma: None. D. Kraskauskas: None. P. Ezouah: None. L. Buckley: None. R. Buzzetti: None. B.W. Van Tassell: None. A. Abbate: None. S. Toldo: None.
- © 2016 by American Heart Association, Inc.