Cardioprotective effects of dietary lipids evident in the time-dependent alterations of cardiac function and gene expression following myocardial infarction.
We have previously shown that prolonged high-saturated fat feeding (SAT) for 8 weeks after myocardial infarction (MI) improves ventricular function and prevents the metabolic remodeling commonly observed in heart failure. The current study was designed to delineate the interplay between markers of energy metabolism and indices of cardiac remodeling with 2 and 4 weeks of post-MI SAT in male Wistar rats. By 2 weeks, less remodeling was noted in MI-SAT evidenced by diminished chamber dilation and greater ejection fraction assessed by echocardiography and hemodynamic measures. In addition, gene expression of energy metabolism targets involved in FA uptake, oxidation, and glucose oxidation regulation was increased in MI-SAT with respect to MI alone, although no change in PDH phosphorylation was observed. The regulatory kinase, phosphoinositide 3 kinase (Pi3k), was strongly induced by 2 weeks in the MI-SAT group, although AKT protein content (a primary downstream target of PI3K that affects metabolism) was decreased by both MI and SAT alone, indicating early involvement of cellular signaling pathways in lipid-mediated cardioprotection. Our results demonstrate that cardioprotection occurs acutely with SAT following MI, with improvement in indices of both cardiac function and fatty acid oxidation, suggesting a mechanistic role for energy metabolism in the beneficial effects of high dietary fat following cardiac injury.
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio.
Jessica M
JM
Berthiaume
Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio.
Salaman M
SM
Azam
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio Department of Medicine, Case Western Reserve University and University Hospitals Case Medical Center, Cleveland, Ohio.
Brian D
BD
Hoit
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio.
Margaret P
MP
Chandler
AKT; PI3K; energy metabolism; gene expression; high dietary fat; left ventricular dysfunction; myocardial infarction; pyruvate dehydrogenase