RGD Reference Report - Uteroplacental insufficiency and reducing litter size alters skeletal muscle mitochondrial biogenesis in a sex-specific manner in the adult rat. - Rat Genome Database

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

Authors: Wadley, GD  Siebel, AL  Cooney, GJ  McConell, GK  Wlodek, ME  Owens, JA 
Citation: Wadley GD, etal., Am J Physiol Endocrinol Metab. 2008 May;294(5):E861-9. doi: 10.1152/ajpendo.00037.2008. Epub 2008 Mar 4.
RGD ID: 10059693
Pubmed: PMID:18319353   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpendo.00037.2008   (Journal Full-text)

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 PPARgamma coactivator-1alpha (PGC-1alpha) 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
placental insufficiency  ISOPpargc1a (Rattus norvegicus)10059693; 10059693mRNA and protein:decreased expression:gastrocnemius muscle (rat)RGD 
placental insufficiency  IEP 10059693mRNA and protein:decreased expression:gastrocnemius muscle (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ppargc1a  (PPARG coactivator 1 alpha)

Genes (Mus musculus)
Ppargc1a  (peroxisome proliferative activated receptor, gamma, coactivator 1 alpha)

Genes (Homo sapiens)
PPARGC1A  (PPARG coactivator 1 alpha)


Additional Information