Abstract 19234: A Short Term Premorbid High Fat Diet Disrupts Cardiac Leptin Signaling, Impairs Glucose Metabolism and Increases Morbidity and Mortality with Myocardial Infarction
Introduction A habitual high fat diet (HFD) contributes to obesity, and increases morbidity in cardiovascular disease (CVD), whereas the effects of a short-term HFD on CVD outcomes are unknown. This study was performed to test the hypothesis that a short term premorbid HFD disrupts cardiac leptin signaling, impairs glucose metabolism and exacerbates morbidity and mortality with myocardial infarction (MI).
Methods/Results Lean, 12 week old male C57BL/6 mice were provided either a HFD (60% fat calories; n=24) or regular chow (RC) (16% fat calories; n=24) for 7 days. Equal number of mice from each dietary group were then randomly assigned to experimental MI or sham procedure, and maintained on RC until study completion at 7 days. Echocardiography and cardiac catheterization were performed on all surviving mice, and hearts were examined for biochemical and histologic measures of cardiac injury, and oxidative metabolism. Results are presented as mean ± SEM with statistical comparisons by t-test, or log-rank Mantel-Cox test (for survival). Groups of sham mice were not significantly different from each other in any measured outcome. However, with MI, a HFD increased mortality (41 vs 19%), cardiac dysfunction (fractional shortening 23±1 vs 29±1% and ejection fraction 24±2 vs 36±2%), and cardiac dilation (end diastolic dimension 4.6±0.1 vs 3.9±0.1mm and volume 56.6±1.3 vs 44.3±2.5uL); all p<0.05. A HFD also increased post-MI cardiac TUNEL positive cells (11.3±0.5 vs 4.1±0.3%; p<0.05) and oxidative stress by thiobarbituric reactive substances (6.8±0.2 vs 4.2±0.3 nMol/ml malondialdehyde equivalents; p<0.05). These worse indices of cardiac injury were associated with a 89±3% reduction in cardiac ObR expression, and a corresponding 86±17% reduction in signal transducer and activator of transcription-3 activation by Western blot (both p<0.05). Finally, post-MI decreases in pyruvate dehydrogenase activity (65±12%), glut4 mRNA (83±2%) and glucose oxidation (69±11%) were seen in hearts from premorbid HFD mice, whereas a 88±9% increase in fatty acid oxidation occurred (all p<0.05).
Conclusions These data suggest that a short-term premorbid HFD impairs cardiac leptin signaling and glucose metabolism, and exacerbates morbidity and mortality outcomes in MI.
- © 2012 by American Heart Association, Inc.