In mice, a maternal high fat diet (mHFD) has been shown to predispose the offspring to develop a cluster of cardio-metabolic risk factors (1, 2). The mHFD could potentially induce its long-term effects by impairing placental function and subsequently fetal development. This study investigates the effect of mHFD on the expression of genes, whose encoded proteins play key roles in placental metabolism such as the endogenous molecular clock network, nutrient transporter proteins, and Sirtuins. Female C57/BL6J mice were maintained under controlled conditions and fed either a HF diet (HF; 45% kcal fat) or standard chow diet (C; 21% kcal fat) 4 weeks before conception and during gestation until E16 when pregnant dams were killed by cervical dislocation and placentas dissected, weighed and stored at -80°C. In the HF and C litters (n=5 and 4, respectively), RNA was extracted from 4 placentas per litter. Quantitative real-time PCR was performed to determine the transcript levels for the circadian clock genes Clock, Bmal1, Cry2 and Per2, the apoptosis associated gene Foxo3A, the deacetylases Sirt1 and Sirt3, the gene marker for lipid transport lipoprotein lipase (Lpl) and the amino acid transporter genes Snat2 and Tat1. Data were normalised using the endogenous control genes Actb and Ywhaz. In the HF group, there were significant reductions in mRNA levels of Snat2, Tat1, Lpl, Bmal1, Sirt1 and Sirt3, compared to C group. In the C group mRNA levels were significantly correlated between all but one gene pair (Cry2 and Bmal1, P = 0.06), whereas in the HF group the overall correlation between genes was lost and only specific sets of genes remained correlated including Sirt1, Tat1 and Snat1 (R > 0.6, P < 0.01 for all pairs). This study demonstrates that a mHFD affects placental mRNA levels for key nutrient transport and regulatory genes. This supports the hypothesis that mHFDs alter placental metabolism to effect fetal development. Metabolic effects of a mHFD on the placenta may be sensed by Sirt1 which is know to interact with the circadian clock system and may also influence regulation of nutrient transporters.