Early Maternal Hyperleptinemia Programs Adipogenic Phenotype in Rats

We have previously reported on the treatment of maternal rats with leptin during the three last days of lactation program for overweight and leptin hypothalamic resistance in the off spring. Here we have investigated whether treatment of maternal rats with leptin in the fi rst ten days of lactation can program metabolic dysfunctions on the adult off spring. Lactating rats were divided into 2 groups: rats (LEP) injected with recom- binant mouse leptin (8 μ g / 100 g / body weight, daily during the fi rst 10 days of lactation) and control group (C) that received the same vol- ume of saline. After weaning, all pups had free access to normal diet, their body weight and food intake were monitored at 4 days interval until 180 days, when they were tested for food intake and response to either leptin (0.5 mg / kg body weight, ip) or saline. The off spring from leptin-treated mothers gained more weight from day 69 onward and had higher food intake from day 145 onward, higher amount of visceral adi- pose tissue (57 % ), higher serum glucose (10 % ), and higher serum leptin (135 % ) at 180 days compared to control group. The food intake was not reduced as expected after acute injection of leptin in these animals, suggesting resistance to the anorexigenic eff ect of leptin. We conclude that maternal hyperleptinemia in early lacta- tion programed higher food intake, body weight gain due to higher total and visceral fat mass, and resistance to anorexigenic eff ect of leptin in the adult off spring even when this hyperleptinemia occurred at the beginning of lactation.