Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation
AUTOR(ES)
Kurtz, David M.
FONTE
The National Academy of Sciences
RESUMO
Abnormalities of fatty acid metabolism are recognized to play a significant role in human disease, but the mechanisms remain poorly understood. Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the initial step in mitochondrial fatty acid oxidation (FAO). We produced a mouse model of LCAD deficiency with severely impaired FAO. Matings between LCAD +/− mice yielded an abnormally low number of LCAD +/− and −/− offspring, indicating frequent gestational loss. LCAD −/− mice that reached birth appeared normal, but had severely reduced fasting tolerance with hepatic and cardiac lipidosis, hypoglycemia, elevated serum free fatty acids, and nonketotic dicarboxylic aciduria. Approximately 10% of adult LCAD −/− males developed cardiomyopathy, and sudden death was observed in 4 of 75 LCAD −/− mice. These results demonstrate the crucial roles of mitochondrial FAO and LCAD in vivo.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=28088Documentos Relacionados
- Synthesis of Long-Chain Acyl-CoA in Chloroplast Envelope Membranes 1
- Functional Analysis of Long-chain Acyl-CoA Synthetase 1 in 3T3-L1 Adipocytes*
- Corresponding increase in long-chain acyl-CoA and acylcarnitine after exercise in muscle from VLCAD mice
- Molecular characterization of inherited medium-chain acyl-CoA dehydrogenase deficiency.
- Suppression of Long Chain Acyl-CoA Synthetase 3 Decreases Hepatic de Novo Fatty Acid Synthesis through Decreased Transcriptional Activity*