Hormonal control of fatty acid oxidation during the neonatal period

Abstract

The development of long-chain fatty acid (LCFA) oxidation, either in the liver for ketone body and energy productions or in peripheral tissues as oxidative fuels, is essential for the newborn mammals. At least in the liver, the postnatal development of LCFA oxidation and ketogenesis seems regulated by pancreatic hormones which plasmatic concentrations are markedly changed at birth (fall in insulin and rise in glucagon levels). In cultured hepatocytes from rabbit fetuses (no LCFA oxidation), the addition of glucagon or cyclic AMP induces LCFA oxidation at a level similar to that found in 24-h-old newborns (high LCFA oxidation). The presence of insulin inhibits totally the effects of glucagon. It seems that carnitine palmitoyltransferase I (CPT I), a key enzyme of LCFA oxidation, represents the main site for hormonal control of LCFA oxidation. This regulation is not due to changes in the hepatic malonyl-CoA concentration (a metabolic intermediate in lipogenesis and a potent inhibitor of CPT I) but to modifications in the sensitivity of CPT I to malonyl-CoA inhibition. The molecular mechanisms responsible for the changes in the sensitivity of CPT I are discussed.