Abstract
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 β-oxidation flux. We therefore hypothesized that gene expression and function of mitochondrial β-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 β-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 β-oxidation and isocitrate dehydrogenase were measured because both enzymes compete for mitochondrial NAD+. Carnitine palmitoyltransferase I, the trifunctional protein of β-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 β-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.
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Abbreviations
- CPTI:
-
carnitine palmitoyltransferase I
- IUGR:
-
intrauterine growth retardation
- AGA:
-
appropriate for gestational age
- ICD:
-
isocitrate dehydrogenase
- MMD:
-
mitochondrial malate dehydrogenase
- ND-4L:
-
NADH-ubiquinone oxidoreductase subunit 4L
- HADH:
-
trifunctional protein of β-oxidation
- HADHA:
-
trifunctional protein of β-oxidation α subunit
- UCP3:
-
uncoupling protein 3
- UCP3l:
-
uncoupling protein 3—long isoform
- UCP3s:
-
uncoupling protein 3—short isoform
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Acknowledgements
The authors thank Dr. Sherin Devaskar for her support and guidance.
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This research was supported, in part, by National Institute of Child Health and Human Development grants P30HD-28836-05 (R.H.L.), 1KO8BD01225-01 (R.H.L.), and 5P30-DK46204-05 (R.H.L.), and the Magee-Womens Hospital Twenty-Five Club.
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Lane, R., Kelley, D., Ritov, V. et al. Altered Expression and Function of Mitochondrial β-Oxidation Enzymes in Juvenile Intrauterine-Growth-Retarded Rat Skeletal Muscle. Pediatr Res 50, 83–90 (2001). https://doi.org/10.1203/00006450-200107000-00016
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DOI: https://doi.org/10.1203/00006450-200107000-00016
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