As stated by the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term conditioning of individual body weight set-point. In particular, maternal obesity, excessive nutrition and accelerated growth in neonates have been shown ta sensitize offspring to obesity and metabolic disturbances. The white adipose tissue (WAT), which develops mainly during lactation in rodents, may represent a prime target of metabolic programming. In order to unravel the unclerlying mechanisms, we have developed a rat model of maternal obesity using a high-fat (HF) diet before and during gestation and lactation. At weaning, offspring from obese clams were fed a standard diet until adulthood. We hypothesize that maternal obesity impairs epigenetic mechanisms and alters offspring's WAT. These modifications might be persistent and have long-term effects on the ex­ pression of adipogenic and lipogenic genes predisposing HF offspring ta fat accumulation. Inthis study, we focused on epigenetic modifications of the leptin gene promoter in WAT of offspring at two stages of lactation (postnatal days 12 (PND12) and 21 (PND21)) and in adulthood (9 months). At birth, newborns from obese clams (callecl HF) were normotrophs. From PND12 ta PND21, HF offspring exhibited a strong increase in adiposity. Higher body weight (+303) observed at weaning persists until 3 months of age. Despite no difference in body weight and energy intake, adult HF offspring showed fat accumulation, glucose intolerance and hyperinsulinemia. During lactation, the expansion of WAT correlatecl with increases in both adipocyte size and number in most depots. The adipose phenotype was still observable in 9-month-olc\ HF offspring. Ma­ ternal obesity led ta markecl changes in adipogenic (PREF-1, C/EBPa, PPARg) and lipogenic (DGAT2, SREBP-1, FAS, leptin) gene expression in WAT of HF adult offspring. In particular, leptin mRNA content was increased in HF offspring in different fat depots at three different stages of development. This is in agreement with persistent elevated plasma leptin levels in HF offspring from weaning ta adulthood. The increased expression of leptin was associated with an enrichment of the acetylation of histone H3, despite an increase of methylation across the promoter region in HF offspring al PND12, PND21 and 9 months of age. Taken together, we showecl that maternal obesity leads ta higher expansion capacity (i.e., hy­ pertrophy and hyperplasia) of offspring's WAT. Increased WAT cellularity was associated with hyperleptinemia and elevated levels of leptin gene expression in HF offspring throughout life. Persistent increased levels of leptin gene expression occur, al least in part, via epigenetic mechanisms which may take place during the early postnatal period.