Bio-Function of Carnitine - Consideration from Analysis of Carnitine-Deficient Mice

SAHEKI Takeyori

doi:10.20632/vso.78.11_545

To learn the bio-function of carnitine, the results on the analysis of carnitine-deficient juvenile visceral steatosis (JVS) mice are reviewed in this paper. JVS mice are an animal model for primary carnitine deficiency, caused by a mutation in Octn2, the gene for plasma membrane carnitine transporter. JVS mice show a variety of symptoms, such as fatty liver, hypoglycemia, hyperammonemia, growth retardation and cardiac hypertrophy. The pathogenesis of the hyperammonemia is unique in that the gene expression of all the urea cycle enzymes is suppressed. Long-chain fatty acids accumulated under cartitine deficiency activate AP-1 DNA binding activity and suppress, for example, the induction of carbamoyl phosphate synthetase (CPS) by glucocorticoid by binding to a novel AP-1 binding site of the CPS gene. The cardiac hypertrophy of JVS mice can be ameliorated by reducing the lipid content of the diet. Under fasted conditions where fat metabolism is activated, JVS mice show reduced locomotor activity and anorexia at refeeding. These symptoms are not only seen in carnitine-deficient JVS mice, but also by administration of an inhibitor of fatty acid metabolism to control mice, indicating that disturbed fatty acid metabolism in general is involved in the symptoms. These results on JVS mice suggest that cartitine plays a role mostly in long-chain fatty acid metabolism and long-chain fatty acids accumulated under carnitine deficiency cause a variety of the symptoms.

Bio-Function of Carnitine - Consideration from Analysis of Carnitine-Deficient Mice

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