• Effects of Dietary Fat Intake on Mitochondrial and Cardiac Function in Heart Failure

      O'Connell, Kelly Anne; Stanley, William C., Ph.D. (2013)
      New treatments are needed for heart failure (HF) and dietary interventions have been suggested as a potential adjunct to current therapies. Recent evidence shows that high fat diets, in the absence of obesity, can improve left ventricular (LV) dysfunction and survival in HF. Mitochondria contribute to HF pathology through impaired oxidative phosphorylation and greater susceptibility to mitochondrial permeability transition (MPT). MPT dissipates membrane potential and triggers cardiomyocyte death. Our lab found that the n3-polyunsaturated fatty acid (n3-PUFA) DHA incorporates into mitochondrial membranes and delays MPT, suggesting that dietary lipids affect mitochondrial phospholipid (PL) composition and function. Survival in HF was prolonged by a high fat diet enriched with long chain saturated fat (LCSat) and monounsaturated fat (MUFA) compared to a high fat diet comprised of a mixture of MUFA+n6-PUFA+n3-PUFA or a low fat diet. The effects of specific dietary fatty acids on the normal and failing heart are complex and poorly understood. Thus, this dissertation 1) compares the effects of low fat/high DHA and high LCSat diets on cardiac and mitochondrial function in healthy animals, and 2) systematically evaluates diets high in MUFA, n6-PUFA or LCSat in pressure overload-induced HF. In Aim 1, normal animals were fed diets rich in DHA or LCSat for 6 weeks. Despite dramatic changes in mitochondrial PL composition and slow mitochondrial Ca<super>2+</super> uptake by the high LCSat diets, there were no effects on mitochondrial respiration or cardiac function. In Aim 2, HF and sham animals were treated with various high fat diets (40% energy as fat) or a standard low fat diet (15% fat) for 15 weeks. There was no evidence of obesity or adverse effects on cardiac structure or function with the various high fat diets. The LCSat diet ameliorated the HF-induced decrease in ejection fraction compared to a standard diet (65% for LCSat vs. 48% for standard). The high MUFA diet conferred the greatest protection from MPT and better maintenance of mitochondrial phospholipid composition in sham rats. In summary, despite dramatic diet-induced differences in mitochondrial PL fatty acid composition, high fat diets had neutral effects on mitochondrial and contractile function.