Uteroplacental insufficiency and reducing litter size alters skeletal muscle mitochondrial biogenesis in a sex-specific manner in the adult rat
Open Access
- 1 May 2008
- journal article
- Published by American Physiological Society in American Journal of Physiology-Endocrinology and Metabolism
- Vol. 294 (5), E861-E869
- https://doi.org/10.1152/ajpendo.00037.2008
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.Keywords
This publication has 42 references indexed in Scilit:
- Placental Restriction of Fetal Growth Increases Insulin Action, Growth, and Adiposity in the Young LambEndocrinology, 2007
- Patients with type 2 diabetes have normal mitochondrial function in skeletal muscleDiabetologia, 2007
- Skeletal Muscle Mitochondrial Functions, Mitochondrial DNA Copy Numbers, and Gene Transcript Profiles in Type 2 Diabetic and Nondiabetic Subjects at Equal Levels of Low or High Insulin and EuglycemiaDiabetes, 2006
- 17beta-estradiol upregulates the expression of peroxisome proliferator-activated receptor alpha and lipid oxidative genes in skeletal muscleJournal of Molecular Endocrinology, 2003
- Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 DiabetesDiabetes, 2002
- Effect of ovarian hormones on mitochondrial enzyme activity in the fat oxidation pathway of skeletal muscleAmerican Journal of Physiology-Endocrinology and Metabolism, 2001
- Fetal and Childhood Growth and Hypertension in Adult LifeHypertension, 2000
- Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscleAmerican Journal of Physiology-Endocrinology and Metabolism, 2000
- The Use of Areas Under Curves in Diabetes ResearchDiabetes Care, 1995
- Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease.BMJ, 1989