Maternal nutritional restriction between early to mid gestation results in greater perirenal adipose tissue deposition in the fetus at term in conjunction with an increased mRNA for the insulin-like growth factors-I and II (Bispham et al 2003). The ability of adipose tissue to take up glucose in conjunction with insulin sensitivity can also contribute to increased fat growth. The aim of the present study was to determine the effect of nutritional restriction on fetal adiposity and expression of key insulin signaling proteins in fetal adipose tissue. Fourteen singleton-bearing sheep of similar body weight and parity were entered into the study. Six of these were nutrient restricted (NR) between 28-80 days gestation and consumed 60% of their total calculated metabolisable energy (ME) requirements for body weight and pregnancy whilst the remainder were fed to appetite (Controls; C) and consumed 150% of calculated ME requirements. After 80 days gestation all ewes were fed to appetite and consumed very similar amounts of feed. At 140 days gestation all sheep were humanely euthanased (IV Na pentobarbitone, 170mg/kg) before fetal adipose tissue sampling. Protein was extracted from adipose tissue and the expression of the insulin receptor β subunit, the p85 regulatory subunit of phosphoinositide (PI) 3- kinase, the p110 β catalytic subunit of PI 3- kinase and the glucose transporter GLUT4 was determined by Western blotting. Results in all cases are given as mean arbitrary unit (AU) ± SEM. Significant differences between groups were assessed by the Students unpaired t-test. A P value of <0.05 was considered statistically significant. Fetuses of NR mothers possessed more perirenal adipose tissue per kg body weight than C (C 3.7 ± 0.2; NR 5.1 ± 0.5 g/kg p<0.05). Protein expression of both the insulin receptor (C 6474 ± 785; NR 11310 ± 1362 AU p<0.01) and p85 (C 38456 ± 2217; NR 44764 ± 1818 AU p<0.05) was significantly increased in NR fetuses. In contrast GLUT 4 (C 34452 ± 4097; NR 36018 ± 2557 au) and p110β (C 17749 ± 1956; NR 21018 ± 1625 AU) protein expression was similar between groups. In conclusion, fetuses of mothers who were nutrient restricted during early pregnancy show increased adiposity compared to controls. This is associated with increased expression of the insulin receptor and regulatory subunit of PI3-kinase. This could contribute to an increase in insulin sensitivity and an increased propensity to store fat.