Faculty Collaboration Database

Altered expression and function of mitochondrial beta-oxidation enzymes in juvenile intrauterine-growth-retarded rat skeletal muscle. Pediatr Res 2001 Jul;50(1):83-90

Date

06/23/2001

Pubmed ID

11420423

DOI

10.1203/00006450-200107000-00016

Scopus ID

2-s2.0-0034984981 (requires institutional sign-in at Scopus site)   57 Citations

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 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.

Author List

Lane RH, Kelley DE, Ritov VH, Tsirka AE, Gruetzmacher EM

MESH terms used to index this publication - Major topics in bold

Animals
Base Sequence
DNA Primers
Enzymes
Female
Fetal Growth Retardation
Gene Expression
Mitochondria, Muscle
Muscle, Skeletal
Oxidation-Reduction
Pregnancy
RNA, Messenger
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Triglycerides