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Unexpected metabolic alterations in VLCAD (very long chain acyl‐CoA dehydrogenase) deficient mouse hearts
Author(s) -
Gélinas Roselle,
Bouchard Bertrand,
ThompsonLegault Julie,
RobillardFrayne Isabelle,
Charron Guy,
Labarthe François,
Des Rosiers Christine
Publication year - 2009
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.23.1_supplement.506.7
Subject(s) - medicine , endocrinology , beta oxidation , enzyme , cardiomyopathy , biology , metabolism , lipid metabolism , lactate dehydrogenase , metabolic disorder , biochemistry , heart failure
Patients with fatty acid oxidation (FAO) defects develop a cardiomyopathy, yet the underlying mechanism is unclear. Using our established working mouse heart model and 13 C‐methodology, we have compared the metabolic phenotype of hearts from VLCAD deficient (VLCAD −/− ) mice, which is the most common FAO disorder in human, and their control VLCAD +/+ counterparts. The expression of selected metabolic genes was also assessed using qPCR. Unexpectedly, 3 month‐old fed or fasted, or 7 month‐old fed VLCAD −/− mouse hearts displayed values for exogenous long chain FAO that were similar to controls, suggesting a compensatory mechanism, although the partitioning of these FA between oxidation and triglycerides was altered in these hearts. Gene expression profiling data revealed little or no difference in the transcript levels for other long chain FAO enzymes (Acadl and Acad9) in 3 or 7 month‐old VLCAD −/− hearts, but that of hormone sensitive lipase (Hsl) was significantly decreased (p<0.001) at 7 months following fasting. Finally, VLCAD −/− hearts showed additional lipid alterations, namely a 30% (p<0.001) decline in docosahexaenoic acid levels in cardiac phospholipids at 3 and 7 months. Collectively, our data highlight unexpected age‐dependent metabolic alterations in VLCAD deficient mouse hearts, which may contribute to cardiomyopathy development. (Supported by NIH & CIHR)