Uteroplacental insufficiency and reducing litter size alters skeletal ...

5 downloads 0 Views 1MB Size Report
Mar 4, 2008 - Garvan Institute of Medical Research, Sydney, New South Wales, ... Research design and methods: Bilateral uterine vessel ligation to induce.
Page 1 Articles of 31 in PresS. Am J Physiol Endocrinol Metab (March 4, 2008). doi:10.1152/ajpendo.00037.2008

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

Glenn D. Wadley1, Andrew L. Siebel1, Greg J. Cooney2, Glenn K. McConell1, Mary E. Wlodek1 and Julie A. Owens3.

1

Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia, 3010.

2

Garvan Institute of Medical Research, Sydney, New South Wales, Australia, 2010. 3School of

Paediatrics and Reproductive Health Discipline of Obstetrics and Gynaecology Faculty of Health Sciences Adelaide University, Australia 5005

Running Head: Altered growth, skeletal muscle and mitochondria

Address for correspondence: Dr. Glenn Wadley, Department of Physiology, The University of Melbourne, Parkville, 3010, Australia. Ph: +61-3-8344-8503, Fax: +61-3-8344-5818, email: [email protected]

Copyright © 2008 by the American Physiological Society.

Page 2 of 31

2

ABSTRACT Objective: 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. Research design and methods: Bilateral uterine vessel ligation to induce uteroplacental insufficiency in the 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 5 at birth (Reduced Litter), which also restricted postnatal growth. Remaining litters from sham mothers were unaltered (Control). Offspring were studied at 6 months of age. Results: In males, both Restricted and Reduced Litter offspring had reduced gastrocnemius PGC-1 mRNA and protein, and mtTFA and COX III mRNA (P