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Uteroplacental insufficiency and reducing litter size alters skeletal muscle mitochondrial biogenesis in a sex-specific manner in the adult rat

Wadley, Glenn D and Siebel, Andrew L and Cooney, Greg J and McConell, Glenn K and Wlodek, Mary E and Owens, Julie A (2008) Uteroplacental insufficiency and reducing litter size alters skeletal muscle mitochondrial biogenesis in a sex-specific manner in the adult rat. American Journal of Physiology - Endocrinology and Metabolism, 294 (5). E861-E869. ISSN 01931849

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Abstract

Uteroplacental insufficiency has been shown to impair insulin action and glucose homeostasis in adult offspring and may act in part via altered mitochondrial biogenesis and lipid balance in skeletal muscle. Bilateral uterine vessel ligation to induce uteroplacental insufficiency in offspring (Restricted) or sham surgery was performed on day 18 of gestation in rats. To match the litter size of Restricted offspring, a separate cohort of sham litters had litter size reduced to five at birth (Reduced Litter), which also restricted postnatal growth. Remaining litters from sham mothers were unaltered (Control). Offspring were studied at 6 mo of age. In males, both Restricted and Reduced Litter offspring had reduced gastrocnemius PPARγ coactivator-1α (PGC-1α) mRNA and protein, and mitochondrial transcription factor A (mtTFA) and cytochrome oxidase (COX) III mRNA (P < 0.05), whereas only Restricted had reduced skeletal muscle COX IV mRNA and protein and glycogen (P < 0.05), despite unaltered glucose tolerance, homeostasis model assessment (HOMA) and intramuscular triglycerides. In females, only gastrocnemius mtTFA mRNA was lower in Reduced Litter offspring (P < 0.05). Furthermore, glucose tolerance was not altered in any female offspring, although HOMA and intramuscular triglycerides increased in Restricted offspring (P < 0.05). It is concluded that restriction of growth due to uteroplacental insufficiency alters skeletal muscle mitochondrial biogenesis and metabolic characteristics, such as glycogen and lipid levels, in a sex-specific manner in the adult rat in the absence of impaired glucose tolerance. Furthermore, an adverse postnatal environment induced by reducing litter size also restricts growth and alters skeletal muscle mitochondrial biogenesis and metabolic characteristics in the adult rat.

Item Type: Article
Uncontrolled Keywords: ResPubID22044. programming, glucose metabolism, intrauterine growth restriction, rats
Subjects: FOR Classification > 0601 Biochemistry and Cell Biology
FOR Classification > 0606 Physiology
Faculty/School/Research Centre/Department > Institute of Sport, Exercise and Active Living (ISEAL)
Depositing User: VUIR
Date Deposited: 24 May 2012 01:50
Last Modified: 12 Feb 2015 03:39
URI: http://vuir.vu.edu.au/id/eprint/8007
DOI: 10.​1152/​ajpendo.​00037.​2008
ePrint Statistics: View download statistics for this item
Citations in Scopus: 20 - View on Scopus

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