Uteroplacental insufficiency and reducing litter size alters skeletal muscle mitochondrial biogenesis in a sex-specific manner in the adult rat.
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.
Wadley
Glenn D
GD
Department of Physiology, The University of Melbourne, Parkville, Australia. gdwadley@unimelb.edu.au
Siebel
Andrew L
AL
Cooney
Greg J
GJ
McConell
Glenn K
GK
Wlodek
Mary E
ME
Owens
Julie A
JA
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006003:Glycogen / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008098:Litter Size / Q000502:physiology*; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology*; D009929:Organ Size / Q000187:drug effects; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010927:Placental Insufficiency / Q000473:pathology*; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D012727:Sex Characteristics; D014157:Transcription Factors / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004268:DNA-Binding Proteins; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D014280:Triglycerides; C422562:mitochondrial transcription factor A; D012313:RNA; D006003:Glycogen; D003576:Electron Transport Complex IV