Background: Diets high in sugar and fat (HSHF) are commonly eaten by women of reproductive age and contribute to the increasing prevalence of obesity during pregnancy. In animals, obesogenic diets fed during pregnancy alter the metabolic phenotype of the adult offspring (1) but little is known about the mechanisms involved prenatally. Preliminary work has shown that feeding a HSHF diet throughout mouse pregnancy increased maternal adiposity, glucose and insulin levels, but reduced insulin like growth factor (IGF-I) and fetal growth (2). This project examined the effect of a HSHF diet on the fat content and expression of proteins involved in insulin/IGF-I signalling and lipid metabolism in the maternal liver, muscle and white adipose tissue (WAT) in late pregnancy. Methods: C57BL6 mice were fed a control diet (energy from fat 11%, sugar 3%) or a HSHF diet (energy; fat 30%, sugar 36%) from day (D)1 of pregnancy (term D20). On D16 and D19, dams were killed and maternal liver, biceps femoralis and retroperitoneal WAT and were dissected and snap frozen for Western blotting. The content of hepatic and muscle fat was measured by the modified Folch method (3). Dietary differences were assessed using ttest and considered significant when, P<0.05. Results: Relative to the control diet, HSHF feeding increased hepatic abundance of specific proteins involved in insulin/IGF signalling in the dam on D16 and D19 (Fig1, P<0.05). In contrast HSHF feeding reduced expression of several proteins involved in this signalling pathway in skeletal muscle (Fig2, P<0.05) and WAT (IGF1R, PI3K p110α/β and p85α, total Akt and pAkt, P<0.03), at both ages. Hepatic lipid metabolic markers were unaffected by HSHF feeding on D16, but PPARα was reduced and LPL, PPARγ, and FAS were increased by D19 (Fig1, P<0.04). In maternal skeletal muscle, a HSHF diet increased expression of FAS on D16, and decreased FATP on both D16 and D19 (Fig2, P<0.05). HSHF diet reduced FATP, PPARα and FAS on D16 and PPARα and FAS on D19 in maternal WAT (P<0.04). The content of fat in maternal liver and muscle was increased by a HSHF diet at D19 (P<0.001) but not day 16. Conclusion: The current study shows that HSHF feeding during mouse pregnancy induces tissue-specific changes in the expression of proteins involved in insulin/IGF signalling and lipid metabolism, consistent with the hyperinsulinaemia and indicative of muscle insulin resistance. These dietary-induced changes in maternal metabolic profile may influence the partitioning of nutrients to fetal growth and thereby explain the intrauterine programming of adult metabolic phenotype.