Neonatal nutritional carnitine deficiency: a piglet model.
The clinical significance of nutritional carnitine deficiency remains controversial. To investigate this condition under controlled conditions, an animal model was developed using the parenterally alimented, carnitine-deprived newborn piglet. Forty-five piglets received total parenteral nutrition for 2-3 wk that was either carnitine-free or supplemented with 100-400 mg/L L-carnitine. Blood and a muscle biopsy were taken at the initial surgery. Carnitine balance studies were performed at 11-14 d of age. Blood, liver, heart, and skeletal muscle were taken at sacrifice for analysis of carnitine, electron microscopy, and oxidation studies. Carnitine-deprived piglets were in negative carnitine balance and had lower blood, urine, and tissue levels of carnitine than carnitine-supplemented animals. There was a positive correlation between excretion and plasma concentrations of free carnitine with an apparent renal threshold between 15 and 35 micromol/L. Plasma levels were correlated with liver and heart, but not muscle, concentrations of total acid-soluble carnitine. Carnitine-deprived piglets had evidence of lipid deposition in liver and skeletal muscle and tended to have a higher incidence of muscle weakness and cardiac failure. Basal rates of oxidation of [14C]palmitate to 14CO2 and 14C-acid-soluble products were lower in liver homogenates from carnitine-deprived piglets than in those from carnitine-supplemented animals and increased in a dose-dependent fashion with the addition of L-carnitine (0, 50, and 500 micromol/L) in vitro. In summary, carnitine deprivation in the neonatal piglet resulted in low carnitine status and morphologic/functional disturbances compatible with carnitine deficiency. The described animal model appears to be suitable for the investigation of neonatal nutritional carnitine deficiency.
Penn
D
D
Department of Pediatrics, Louisiana State University Medical Center, New Orleans 70112, USA.
Bobrowski
P J
PJ
Zhang
L
L
Schmidt-Sommerfeld
E
E
D000818:Animals; D000831:Animals, Newborn; D002331:Carnitine / Q000172:deficiency* / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D010084:Oxidation-Reduction; D013552:Swine; D014018:Tissue Distribution
D005227:Fatty Acids; D002331:Carnitine