Myocardial carnitine palmitoyltransferase I expression and long-chain fatty acid oxidation in fetal and newborn lambs.
Carnitine palmitoyltransferase I (CPT I) catalyzes the conversion of acyl-CoA to acylcarnitine at the outer mitochondrial membrane and is a key enzyme in the control of long-chain fatty acid (LC-FA) oxidation. Because myocardial LC-FA oxidation increases dramatically after birth, we determined the extent to which CPT I expression contributes to these changes in the perinatal lamb. We measured the steady-state level of transcripts of the CPT1A and CPT1B genes, which encode the liver (L-CPT I) and muscle CPT I (M-CPT I) isoforms, respectively, as well as the amount of these proteins, their total activity, and the amount of carnitine in left ventricular tissue from fetal and newborn lambs. We compared these data with previously obtained myocardial FA oxidation rates in vivo in the same model. The results showed that CPT1B was already expressed before birth and that total CPT I expression transiently increased after birth. The protein level of M-CPT I was high throughout development, whereas that of L-CPT I was only transiently upregulated in the first week after birth. The total CPT I activity in vitro also increased after birth. However, the increase in myocardial FA oxidation measured in vivo (112-fold) by far exceeded the increase in gene expression (2.2-fold), protein amount (1.1-fold), and enzyme activity (1.2-fold) in vitro. In conclusion, these results stress the importance of substrate supply per se in the postnatal increase in myocardial FA oxidation. M-CPT I is expressed throughout perinatal development, making it a primary target for metabolic modulation of myocardial FA oxidation.
Bartelds
Beatrijs
B
Dept. of Pediatrics, University of Groningen, Research Lab CMCV-2, Hanzeplein 1, NL-9713 GZ Groningen, The Netherlands.
Takens
Janny
J
Smid
Gioia B
GB
Zammit
Victor A
VA
Prip-Buus
Carina
C
Kuipers
Jaap R G
JR
van der Leij
Feike R
FR
D000818:Animals; D000831:Animals, Newborn; D002331:Carnitine / Q000378:metabolism; D002334:Carnitine O-Palmitoyltransferase / Q000235:genetics* / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D006321:Heart / Q000196:embryology* / Q000502:physiology; D009206:Myocardium / Q000201:enzymology*; D010084:Oxidation-Reduction; D011247:Pregnancy; D012756:Sheep
D005227:Fatty Acids; D002334:Carnitine O-Palmitoyltransferase; D002331:Carnitine