Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep

1 Discipline of Physiology, School of Molecular and Biomedical Sciences, The University of Adelaide, South Australia; 2 Commonwealth Scientific and Industrial Research Organisation Livestock Industries, Queensland Biosciences Precinct, St. Lucia, Queensland; and, 3 Early Origins of Adult Health Research Group, Sansom Research Institute, School of Pharmacy and Medical Sciences, University of South Australia, South Australia, Australia Submitted 29 October 2007 ; accepted in final form 11 February 2008 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- , retinoid-X-receptor- ], 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 P O 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. placenta; leptin; obesity Address for reprint requests and other correspondence: I. C. McMillen, Early Origins of Adult Health Research Group, Sansom Research Institute, School of Pharmacy and Medical Sciences, Univ. of South Australia, South Australia 5005, Australia (e-mail: caroline