Impact of embryo number and periconceptional undernutrition on factors regulating adipogenesis, lipogenesis, and metabolism in adipose tissue in the sheep fetus.
Maternal undernutrition around the time of conception is associated with an increased risk of insulin resistance in adulthood. We hypothesized that maternal undernutrition during the periconceptional (PCUN: -60 to 7 days) and/or preimplantation (PIUN: 0-7 days) periods would result in a decrease in UCP1 expression and the abundance of insulin signaling molecules and an increase in the abundance of factors that regulate adipogenesis and lipogenesis in fetal perirenal adipose tissue (PAT) and that these effects would be different in singletons and twins. Maternal PCUN and PIUN resulted in a decrease in UCP1 expression in PAT, and PIUN resulted in higher circulating insulin concentrations, an increased abundance of pPKCζ and PDK4, and a decreased abundance of Akt1, phosphorylated mTOR, and PPARγ in PAT in singleton and twin fetuses. In singletons, there was also a decrease in the abundance of p110β in PAT in the PCUN and PIUN groups and an increase in total AMPKα in PAT in the PIUN group. In twins, however, there was an increase in the abundance of mTOR in the PCUN group and an increase in PDK2 and decrease in total AMPKα in the PIUN group. Thus exposure to periconceptional undernutrition programs changes in the thermogenic capacity and the insulin and fatty acid oxidation signaling pathway in visceral fat, and these effects are different in singletons and twins. These findings are important, as the thermogenic capacity of brown fat and the insulin sensitivity of visceral fat are important determinants of the risk of developing obesity and an insulin resistance phenotype in later life.
Sansom Institute for Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia;
Shervi
S
Lie
Janna L
JL
Morrison
Olivia
O
Williams-Wyss
Susan E
SE
Ozanne
Song
S
Zhang
Simon K
SK
Walker
David O
DO
Kleemann
Severence M
SM
MacLaughlin
Claire T
CT
Roberts
I Caroline
IC
McMillen
D050156:Adipogenesis; D000818:Animals; D017849:Animals, Inbred Strains; D001315:Australia; D005260:Female; D005306:Fertilization; D047109:Fetal Development; D018507:Gene Expression Regulation, Developmental; D006946:Hyperinsulinism / Q000196:embryology / Q000209:etiology; D050152:Intra-Abdominal Fat / Q000196:embryology / Q000378:metabolism*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D050155:Lipogenesis; D008098:Litter Size; D044342:Malnutrition / Q000503:physiopathology*; D039382:Maternal Nutritional Physiological Phenomena; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D034561:Sheep, Domestic; D015398:Signal Transduction; D000071256:Uncoupling Protein 1
D007473:Ion Channels; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D000071256:Uncoupling Protein 1
metabolism; nutrition; pregnancy; programming