Maternal obesity eliminates the neonatal lamb plasma leptin peak

Non technical summary Leptin, an adipose tissue hormone, inhibits the brain's central drive to eat, enabling maintenance of normal body weight and composition. The leptin peak present in newborn rodents controls development of brain appetite regulatory areas, and alteration in its timing and amplitude predisposes to obesity in later life. However, unlike humans, rodents are born at an immature stage of development so to determine potential relevance to human development, we examined the leptin peak in newborn lambs, born at a more advanced level of maturity equivalent to humans. The normal peak was absent in lambs born to obese mothers who showed higher newborn levels of plasma cortisol. We conclude that similarities and differences exist in neonatal leptin in species born immature or mature. This information aids understanding of effects of the obesity epidemic in women on their offspring and will help promote diagnosis, prevention and therapy.A neonatal peak in rodent plasma leptin plays a central role in regulating development of the hypothalamic appetite control centres. Maternal obesity lengthens and amplifies the peak in altricial rodent species. The precise timing and characteristics of the neonatal leptin peak have not been established in offspring of either normal or obese mothers in any precocial species. We induced obesity by feeding female sheep for 60 days before conception, and throughout pregnancy and parturition with 150% of the diet consumed by control ewes fed to National Research Council recommendations. We have reported that mature offspring of obese sheep fed similarly exhibited increased appetite, weight gain and obesity in response to ad libitum feeding at 19 months of age. We observed a leptin peak in lambs of control ewes between days 6 and 9 of postnatal life, earlier than reported in rodents. This peak was not present in lambs born to obese ewes. The leptin peak in lambs born to control ewes was not clearly related to any changes in plasma cortisol, insulin, triiodothyronine, IGF-1 or glucose. However, there was a significant increase in cortisol at birth in lambs born to obese ewes related to an increase in leptin in the first day of life. We conclude that the increased cortisol seen in lambs of obese sheep plays a role in disrupting the normal peak of leptin in lambs born to obese ewes thereby predisposing them to increased appetite and weight gain in later life.