Abstract
Uteroplacental insufficiency and subsequent intrauterine growth retardation (IUGR) increase the risk of insulin resistance in humans and rats. Aberrant skeletal muscle lipid metabolism contributes to the pathogenesis of insulin resistance. Peroxisome proliferator-activated receptor-γ co-activator-1 (PGC-1) is a transcriptional co-activator that affects gene expression of key lipid metabolizing enzymes such as carnitine palmitoyl-transferase I (mCPTI). Because gene expression of lipid metabolizing enzymes is altered in IUGR postnatal skeletal muscle, and we hypothesized that PGC-1 expression would be similarly affected. To prove this hypothesis, bilateral uterine artery ligation and sham surgery were used to produce IUGR and control rats respectively. Western Blotting demonstrated that PGC-1 hind limb skeletal muscle protein levels were increased in perinatal and postnatal IUGR rats. Conventional RT-PCR demonstrated that PGC-1 mRNA levels were similarly increased in perinatal hind limb skeletal muscle and juvenile extensor digitorum longus (EDL), but were decreased in juvenile soleus. Because a gender specific trend was noted in PGC-1 mRNA levels, real time RT-PCR was used for further differentiation. Real time RT-PCR revealed that changes in postnatal skeletal muscle PGC-1 expression were more marked in male IUGR rats versus female IUGR rats. Down stream targets of PGC-1 followed a similar pattern of expression. We conclude that PGC-1 expression is altered in rat IUGR skeletal muscle and speculate that it contributes to the pathogenesis of insulin resistance in the IUGR rat.
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Abbreviations
- CD36:
-
fatty acid translocase
- CoxIV:
-
cytomchrome c oxidase subunit I
- EDL:
-
extensor digitorum longus
- IUGR:
-
intrauterine growth retardation
- mCPTI:
-
muscle isoform of carnitine palmitoyl-transferase I
- mTFA:
-
mitochondrial transcription factor A
- NRF-1:
-
nuclear respiratory factor 1
- PGC-1:
-
peroxisome proliferator-activated receptor-γ coactivator-1
- UCP-2:
-
uncoupling protein 2
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National Institute of Child Health and Human Development Grant K08-BD-01225-1, R01 HD41075 and an American Diabetes Association Grant supported this work.
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Lane, R., MacLennan, N., Daood, M. et al. IUGR Alters Postnatal Rat Skeletal Muscle Peroxisome Proliferator-Activated Receptor-γ Coactivator-1 Gene Expression in a Fiber Specific Manner. Pediatr Res 53, 994–1000 (2003). https://doi.org/10.1203/01.PDR.0000064583.40495.51
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DOI: https://doi.org/10.1203/01.PDR.0000064583.40495.51
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