Altered expression and function of mitochondrial beta-oxidation enzymes in juvenile intrauterine-growth-retarded rat skeletal muscle.
Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) affects postnatal metabolism. In juvenile rats, IUGR alters skeletal muscle mitochondrial gene expression and reduces mitochondrial NAD(+)/NADH ratios, both of which affect beta-oxidation flux. We therefore hypothesized that gene expression and function of mitochondrial beta-oxidation enzymes would be altered in juvenile IUGR skeletal muscle. To test this hypothesis, mRNA levels of five key mitochondrial enzymes (carnitine palmitoyltransferase I, trifunctional protein of beta-oxidation, uncoupling protein-3, isocitrate dehydrogenase, and mitochondrial malate dehydrogenase) and intramuscular triglycerides were quantified in 21-d-old (preweaning) IUGR and control rat skeletal muscle. In isolated skeletal muscle mitochondria, enzyme function of the trifunctional protein of beta-oxidation and isocitrate dehydrogenase were measured because both enzymes compete for mitochondrial NAD(+). Carnitine palmitoyltransferase I, the trifunctional protein of beta-oxidation, and uncoupling protein 3 mRNA levels were significantly increased in IUGR skeletal muscle, whereas mRNA levels of isocitrate dehydrogenase and mitochondrial malate dehydrogenase were unchanged. Similarly, trifunctional protein of beta-oxidation activity was increased in IUGR skeletal muscle mitochondria, and isocitrate dehydrogenase activity was unchanged. Interestingly, skeletal muscle triglycerides were significantly increased in IUGR skeletal muscle. We conclude that uteroplacental insufficiency alters IUGR skeletal muscle mitochondrial lipid metabolism, and we speculate that the changes observed in this study play a role in the long-term morbidity associated with IUGR.
Lane
R H
RH
Department of Pediatrics, UCLA School of Medicine, Mattel Children's Hospital at UCLA, Los Angeles, California 90095, USA. rlane@mednet.ucla.edu
Kelley
D E
DE
Ritov
V H
VH
Tsirka
A E
AE
Gruetzmacher
E M
EM
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation; D015870:Gene Expression; D008931:Mitochondria, Muscle / Q000201:enzymology*; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D010084:Oxidation-Reduction; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
D017931:DNA Primers; D004798:Enzymes; D012333:RNA, Messenger; D014280:Triglycerides