When pups issued from obese dams were assigned to the chow diet at weaning, they displayed inherited defective leptin signaling in hypothalamus, which persisted until age of 6 months despite normal body weight evolution. However, pups born to obese P dams and weaned on the same P diet were not protected against diet induced obesity. Clearly the two inappropriate HF and P diets have distinct impacts on both dams and pups, likely in relation with their different palatability or composition. Both diets were then used in order to study whether adult pups born to HF dams and weaned on a chow diet, will be more or less susceptible than control rats to develop obesity when switched to the obesogenic P diet, a question that remained unresolved in our previous study. Thus, male and female offspring born to HF or control dams were assigned to the control diet for 7 postweaning weeks, and then switched to the P diet for 3 additional months. Our results clearly showed that offspring from both genders born to HF dams were protected from the obesogenic effect of P diet as their body weight gain was lower as compared to offspring born to chow dams. In addition, the potential protective effect of maternal HF diet involves most likely different genderdependent mechanisms. Daily energy intakes and final physiological EX 527 parameters measured in adult fasted rats are shown in Table 2. Mean daily energy intakes were calculated from daily food intakes measured twice a week from the 2nd to the 6th postweaning week on 10 cages of 2 rats per group. The highest value was found in the PC group of rats fed the highly palatable P diet and born to normally fed dams. Their counterparts born to obese dams ingested less energy for a similar weight gain, suggesting a better food Nutlin-3 efficacy of the P diet in this group. The maternal diet did not affect CC and CP rats, which both displayed a lean phenotype while their energy intake was close to that of obese PP rats. As observed in Figure 3, independently of maternal diet a striking effect of the post-weaning diet appeared on the body weight evolution and gain. The same conclusion was drawn by comparing plasma concentrations of triglycerides, leptin and insulin, all reported in Table 2. These parameters were higher in rats fed the P diet than in rats fed the chow diet. The only differences concerned the plasma levels of leptin which were lower in CP rats than in control CC rats, and the plasma levels of insulin and HOMA index of PP rats which overpassed those of PC rats. In addition, the lowest plasma cholesterol value was found in PP rats, indicating a longterm impact of the maternal metabolic status on these parameters. The body weight measured after 7 post-weaning weeks on the chow diet is presented in Table 3 for the 4 groups of adult offspring.