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Adipocyte cytokine leptin plays the key role in energy homeostasis regulation: it inhibits food intake and increases energy expenditure.In pregnancy, leptin was suggested to have programming effects on fetus development.Both malnutrition and maternal obesity in pregnancy predispose offspring to become obese although malnutrition is characterized with decrease and obesity with increase of leptin blood levels.The question arises: what role (if any)does leptin play in developmental programming during pregnancy.To answer this question, we used the genetic model with enhanced leptin level during pregnancy (mutation "yellow" at the mouse agouti locus (Ay) increases blood leptin levels during pregnancy without effects on other metabolic characteristics [Makarova et al., 2010]).Measurements: food intake and body weight gain after weaning, glucose tolerance, levels of glucose and insulin in blood, hypothalamic sensitivity to leptin in maturity were measured in mail and female progeny of primiparous Ay/a (enhanced leptin during pregnancy) and a/a (control) C57Bl/6J mice.Results: Enhanced leptin levels during pregnancy (Ay/a mothers) influenced on male progeny and did not influence on female progeny development.In males, increased maternal leptin during pregnancy was associated with changes in food intake, body weight, and glucose metabolism regulation.Ay/a as compared to a/a mother sons had decreased weight gain after weaning.In maturity, they had increased blood insulin levels after food deprivation and unchanged blood glucose levels both in rest conditions and during glucose tolerance test, they consumed more food in control conditions and less food during refeeding after food deprivation.At the same time, maternal leptin did not influence on hypothalamic expression of orexigenic neuropeptides NPY and AgRP.Maternal leptin inhibited sensitivity of male progeny to exogenous leptin.Leptin insensitivity of Ay/a mouse sons was associated with unchanged hypothalamic expression of ObRb, POMC, and AgRP.It may result from increased leptin elimination from blood because blood leptin levels were lower in Ay/a as compared to a/a mother sons within 24h after leptin injections.Conclusion: Enhanced leptin levels in pregnant mice influence on development of systems which regulate glucose metabolism and energy homeostasis in male progeny, bias energy balance toward catabolism and, possibly, counteract development of obesity.