Abstract 17213: A High Leucine Diet Stimulates Cardiac Leptin Production and Attenuates Ischemic Myocardial Injury in Mice
Introduction: Leucine is an essential amino acid that stimulates adipose production of leptin. In myocardial infarction (MI), leptin provides cardioprotection by improving survival, and limiting structural and functional injury. This study was thus performed to test the hypothesis that a high leucine diet (HLD) will increase circulating leptin, activate cardiac leptin signaling, and in the setting of MI, attenuate injury.
Methods: 8 week old male C57BL/6J mice were provided either a HLD (5% by weight; n=12) or regular chow (1.5% leucine by weight; n=12) for 7 days. An equal number of mice from each dietary group were then randomly assigned to experimental MI or sham procedure. Diets were then continued for 7 more days, at which time blood was drawn for leptin ELISA, echocardiography and cardiac catheterization were completed, and mice were sacrificed. Hearts were processed for mRNA (quantitative RT-PCR) and protein analyses (Western blotting).
Results: are presented as mean change ± SEM with statistical comparisons by t-test (for 2 groups) or ANOVA (for >2 groups).
Results: There was no significant difference in weight between the dietary or surgical groups of mice (p>0.05). However, leptin mRNA was increased 2.1±0.2 fold in fat, and 17.5±1.1 fold in the heart of animals on a HLD (both p<0.05). In mice on a regular diet, circulating leptin was elevated post-MI (1.5±0.2 vs. 3.0±0.2 ng/ml, p<0.05). With a HLD, both sham (4.0±0.3 ng/ml) and MI (4.5±0.4 ng/ml) groups showed additional increases in leptin (both p<0.05 vs regular diet sham). A 3.1±0.1 fold activation of cardiac signal transducer and activator of transcription (STAT)-3 protein was seen in mice on a regular diet post-MI (p<0.05). With a HLD, STAT3 was further activated in sham mice (4.8±0.1 fold) and post-MI (6.9±0.7 fold) (both p<0.05 vs regular diet sham). Finally, mice on a HLD showed attenuated cardiac injury post-MI, with smaller left ventricular (LV) end diastolic dimension (4.1±0.1 vs 4.5±0.1 mm) and volume (73.5±1.8 vs 83.5±1.2 L), and greater LV fractional shortening (34±1 vs 29±1 %) and ejection fraction (37±2 vs 31±1 %); all p<0.05.
Conclusions: Dietary leucine and MI both increase circulating leptin and activate cardiac STAT3, resulting in improved structural and functional outcomes post-MI.
- © 2010 by American Heart Association, Inc.