In the liver, the expression level of phosphotyrosine phosphatase 1B was significantly increased in PH group as high content screening compared to the other groups, and a similar effect was found for the expression of adiponectin receptors 1 and 2. Insulin receptor expression was significantly reduced in CH group as compared to the others. In female offspring, hypothalamic expression of POMC and NPY was affected by maternal diet independently of offspring diet and expression of Obrb was only increased in PC group whereas UCP2 expression was not affected. In liver, no significant change was observed for PTP-1B, IR, AdipoR1 or AdipoR2. Since high fat diet given to dams seemed to deeply affect the offspring energy homeostasis, we hypothesized that this could be associated to changes in hypothalamic and more precisely in arcuate nucleus organization. The immunohistochemical detection in the ARC revealed that the maternal HF diet induced a significant increase in the density of astrocytic processes around the blood vessels in males at weaning whereas this alteration was not observed in females. This genderspecific modification was maintained until adulthood. It is to notice that the maternal HF diet had no effect on the vascularisation or the global astrocyte LY2835219 coverage in the ARC, whatever the gender. The highly palatable P diet used in the present study has been initally presented as an alternative to the classical cafeteria diet to promote a massive obesity. Thus the P diet induced a massive obesity in dams, which was persistent from before mating and throughout gestation and lactation as pups were reared in large litters. At weaning, pups born to P dams exhibited slight growth retardation as compared with those born to control dams. This observation might be surprising since stress is likely minimized in pups weaned on day 28, which progressively complete milk by the maternal solid food, as under natural conditions. For comparison with our previous study, dams fed the HF diet only presented a slight overweight before mating, followed by a spectacular body weight loss during the lactation period and weaning pups weighed 10% less than those of normally fed dams. Using a HF diet based also on vegetal oil, others reported that gestation/lactation alleviate some of the effect of HF feeding on body weight gain of dams compared to nonpregnant rats but at day 20, pups reared in small litters appeared heavier and fatter, and considered to be more predisposed to obesity. Among the four groups of adult male rats born to C or P dams and weaned on the C or P diet, only the control CC group exhibited an increased phosphorylation level of both STAT3 and ERK1/2 in the hypothalamus in response to leptin challenge. It may be concluded that in the three other groups, a central leptinresistance was either induced by the post-weaning P diet and/or programmed by the maternal P diet. Interestingly, only rats fed the post-weaning P diet were overtly obese with classical associated traits of the metabolic syndrome, such as hyperglycemia, hypertriglyceridemia, hyperinsulinemia and hyperleptinemia on fasting state.