Enhancement of activities relative to fatty acid oxidation in the liver of rats depleted of L-carnitine by D-carnitine and a gamma-butyrobetaine hydroxylase inhibitor.
This study was designed to examine whether the depletion of L-carnitine may induce compensatory mechanisms allowing higher fatty acid oxidative activities in liver, particularly with regard to mitochondrial carnitine palmitoyltransferase I activity and peroxisomal fatty acid oxidation. Wistar rats received D-carnitine for 2 days and 3-(2,2,2,-trimethylhydrazinium)propionate (mildronate), a noncompetitive inhibitor of gamma-butyrobetaine hydroxylase, for 10 days. They were starved for 20 hr before being sacrificed. A dramatic reduction in carnitine concentration was observed in heart, skeletal muscles and kidneys, and to a lesser extent, in liver. Triacylglycerol content was found to be significantly more elevated on a gram liver and whole liver basis as well as per mL of blood (but to a lesser extent), while similar concentrations of ketone bodies were found in the blood of D-carnitine/mildronate-treated and control rats. In liver mitochondria, the specific activities of acyl-CoA synthetase and carnitine palmitoyltransferase I were enhanced by the treatment, while peroxisomal fatty acid oxidation was higher per gram of tissue. It is suggested that there may be an enhancement of cellular acyl-CoA concentration, a signal leading to increased liver fatty acid oxidation in acute carnitine deficiency.
Tsoko
M
M
Laboratoire de Nutrition Cellulaire et Métabolique, EA DRED 564, Faculté des Sciences, Dijon, France.
Beauseigneur
F
F
Gresti
J
J
Niot
I
I
Demarquoy
J
J
Boichot
J
J
Bezard
J
J
Rochette
L
L
Clouet
P
P
D000818:Animals; D001835:Body Weight; D002331:Carnitine / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000172:deficiency*; D005227:Fatty Acids / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008763:Methylhydrazines / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D009929:Organ Size; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D050563:gamma-Butyrobetaine Dioxygenase
D005227:Fatty Acids; D008763:Methylhydrazines; C050147:3-(2,2,2-trimethylhydrazine)propionate; D006899:Mixed Function Oxygenases; D050563:gamma-Butyrobetaine Dioxygenase; D002331:Carnitine