title: Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep.
abstract: Placental restriction (PR) of fetal growth results in a low birth weight and an increased visceral fat mass in postnatal life. We investigated whether PR alters expression of genes that regulate adipogenesis [IGF1, IGF1 receptor (IGF1R), IGF2, IGF2R, proliferator-activated receptor-gamma, retinoid-X-receptor-alpha], adipocyte metabolism (lipoprotein lipase, G3PDH, GAPDH) and adipokine signaling (leptin, adiponectin) in visceral adipose tissue before birth. PR was induced by removal of the majority of endometrial caruncles in nonpregnant ewes before mating. Fetal blood samples were collected from 116 days gestation, and perirenal visceral adipose tissue (PAT) was collected from PR and control fetuses at 145 days. PAT gene expression was measured by quantitative RT-PCR. PR fetuses had a lower weight (PR 2.90 +/- 0.32 kg; control, 5.12 +/- 0.24 kg; P < 0.0001), mean gestational arterial Po(2) (P < 0.0001), plasma glucose (P < 0.01), and insulin concentrations (P < 0.02), than controls. The expression of IGF1 mRNA in PAT was lower in the PR fetuses (PR, 0.332 +/- 0.063; control, 0.741 +/- 0.083; P < 0.01). Leptin mRNA expression in PAT was also lower in PR fetuses (PR, 0.077 +/- 0.009; control, 0.115 +/- 0.013; P < 0.05), although there was no difference in the expression of other adipokine or adipogenic genes in PAT between PR and control fetuses. Thus, restriction of placental and hence, fetal substrate supply results in decreased IGF1 and leptin expression in fetal visceral adipose tissue, which may alter the functional development of the perirenal fat depot and contribute to altered leptin signaling in the growth-restricted newborn and the subsequent emergence of an increased visceral adiposity.
authors.affiliation: Discipline of Physiology, School of Molecular and Biomedical Sciences, The University of Adelaide, SA, Australia.
authors.forename: Jaime A
authors.initials: JA
authors.lastname: Duffield
authors.forename: Tony
authors.initials: T
authors.lastname: Vuocolo
authors.forename: Ross
authors.initials: R
authors.lastname: Tellam
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Yuen
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Muhlhausler
authors.forename: I Caroline
authors.initials: IC
authors.lastname: McMillen
mesh_terms: D052242:Adiponectin / Q000096:biosynthesis; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018076:DNA, Complementary / Q000096:biosynthesis; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D005333:Fetus / Q000378:metabolism*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000096:biosynthesis; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis; D007668:Kidney / Q000378:metabolism; D020738:Leptin / Q000096:biosynthesis*; D008071:Lipoprotein Lipase / Q000096:biosynthesis; D010100:Oxygen / Q000097:blood; D047495:PPAR gamma / Q000096:biosynthesis; D010927:Placental Insufficiency / Q000503:physiopathology*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis*; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D017527:Receptor, IGF Type 2 / Q000096:biosynthesis; D047490:Retinoid X Receptor alpha / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D018076:DNA, Complementary; D005230:Fatty Acids, Nonesterified; D020738:Leptin; D047495:PPAR gamma; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D047490:Retinoid X Receptor alpha; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D017526:Receptor, IGF Type 1; D008071:Lipoprotein Lipase; D010100:Oxygen