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Enhanced Mitochondrial Function in High Fat Fed Heart Failure Animals is Due to Increased Activation of Medium‐Chain Acyl‐CoA Dehydrogenase
Author(s) -
Rennison Julie H,
McElfresh Tracy A,
Patel Hiral V,
Foster Amy B,
Patel Kalpana K,
Young Martin E,
Hoppel Charles L,
Chandler Margaret P
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a666-d
Subject(s) - medicine , endocrinology , beta oxidation , palmitoylcarnitine , chemistry , mitochondrion , dehydrogenase , enzyme , respiration , fatty acid , heart failure , carnitine , biology , metabolism , biochemistry , botany
Administration of a high fat in heart failure (HF) increased mitochondrial respiration and did not alter left ventricular (LV) function. PPARα 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 β‐oxidation enzymes (short, medium (MCAD), and long chain acyl‐CoA dehydrogenase). Rats underwent ligation or sham surgery and were fed normal (10% kcal fat) (SHAM NC, HF NC) or high fat diet (60% kcal saturated fat) (SHAM FAT, HF FAT) for 8 weeks. Subsarcolemmal mitochondria were isolated from the LV. State 3 respiration using fatty acid substrates octanoylcarnitine and palmitoylcarnitine increased in HF FAT compared to SHAM FAT and HF NC respectively (242±21, 246±21 vs 183±8, 181±6 and 193±17, 185±16 nAO/min/mg). Despite decreased mcad in HF NC and HF FAT, MCAD activity increased in HF FAT (65.1±2.7 vs 81.5±5.4 nmoles/min/mg). Activity of each chain length specific acyl‐CoA dehydrogenase correlated to increased state 3 respiration. MCAD protein was not altered by HF or high fat. In conclusion, enhanced mitochondrial respiration associated with high fat may result from increased activation of β‐oxidation enzymes, but is not due to increased mRNA expression of these genes. High fat had no effect in normal rats. (Grant # NIH HL‐081857 & AHA SDG 0535361N)