Abstract 851: High Saturated Fat Feeding Prevents Left Ventricular Dysfunction and Enhances Mitochondrial Function in Heart Failure
Accumulation of lipids in the heart is associated with contractile dysfunction, and has been proposed to be a causative factor in mitochondrial dysfunction. We have previously shown that administration of a high saturated fat diet in heart failure (HF) increased mitochondrial respiration and ETC complex activities and did not adversely affect left ventricular (LV) contractile function. We hypothesized that the elevated mitochondrial respiration in high saturated fat fed HF animals is due to increased activation of PPARα regulated genes (medium chain acyl CoA dehydrogenase (MCAD), and mitochondrial thioesterase-1 (MTE-1)) involved in fatty acid utilization. Rats underwent coronary artery ligation or sham surgery and were fed normal (10% kcal from fat) (SHAM+NC, n=9, HF+NC, n=10) or high saturated fat diet (60% kcal from saturated fat) (SHAM+SAT, n=9, HF+SAT, n=10) for 8 weeks. LV function was assessed by echocardiography and LV catheterization. Subsarcolemmal (SSM) and interfibrillar mitochondria were isolated from the LV and mitochondrial respiration was assessed. Saturated fat feeding alone did not affect LV hypertrophy or contractility, but in HF it decreased biventricular/body weight ratio (BV/BW) and increased peak LV +dP/dt (Table⇓). Fractional shortening area was decreased with HF but responded similarly during dobutamine stress in both HF groups. State 3 respiration in the SSM was increased in HF+SAT compared to SHAM+SAT and HF+NC using fatty acid substrates octanoylcarnitine and palmitoylcarnitine. Whereas MCAD activity was unchanged with HF, mRNA expression of mcad and mte1 were decreased in HF+NC. Despite no increase in mcad and mte1 in HF+SAT, MCAD activity was elevated in the SSM. In conclusion, the enhanced mitochondrial respiration and LV contractile function associated with high saturated fat feeding may result from increased activation of the fatty acid oxidation pathway. Interestingly, high fat feeding had no effect in normal rats.