Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: 4/18/2007
Publication Date: 6/18/2007
Citation: Rennison, J.H., Young, M.E., Hoppel, C.L., Chandler, M.P. 2007. High fat fed heart failure animals have enhanced mitochondrial function and acyl-coa dehydrogenase activities [abstract]. 5th Annual Conference of the Society for Heart and Vascular Metabolism. p. 1. Interpretive Summary:
Technical Abstract: We have previously shown that administration of high fat in heart failure (HF) increased mitochondrial respiration and did not alter left ventricular (LV) function. PPARalpha is a nuclear transcription factor that activates expression of genes involved in fatty acid uptake and utilization. We hypothesized that elevated mitochondrial respiration in high fat fed HF rats is due to increased expression of Beta-oxidation enzymes (short (SCAD), medium (MCAD), and long (LCAD) chain acyl-CoA dehydrogenase). Rats underwent ligation or sham surgery and were fed normal (10% kcal fat) (SHAM, HF) or high fat diet (60% kcal saturated fat) (SHAM+FAT, HF+FAT) for 8 weeks. Subsarcolemmal and interfibrillar mitochondria were isolated from the LV. State 3 respiration using fatty acid substrates octanoylcarnitine and palmitoylcarnitine was increased in HF+FAT compared to SHAM+FAT and HF respectively (242 +/- 21, 246 +/- 21 vs 183 +/- 8, 181 +/- 6 and 193 +/- 17, 185 +/- 16 nAO/min/mg). Despite decreased mcad mRNA in HF and HF+FAT, MCAD protein was not different between groups, and MCAD activity increased in HF+FAT (65.1 +/- 2.7 vs 81.5 +/- 5.4 nmoles/min/mg). Activities of SCAD and LCAD were also elevated in HF+FAT though scad and lcad rnRNA expression were not different. SCAD, MCAD, and LCAD activities correlated to increased state 3 respiration using both fatty acid substrates. In conclusion, enhanced mitochondrial respiration associated with high fat may result from increased activation of acyl-CoA dehydrogenases, but is not due to increased mRNA or protein expression. High fat in normal animals did not adversely affect mitochondrial respiration or the expression and activity of enzymes involved in Beta-oxidation.