Multigenerational impact of maternal overnutrition/obesity in the sheep on the neonatal leptin surge in granddaughters

Background/objectives: We have reported that maternal overnutrition/obesity (OB) in sheep resulting from feeding 150% of National Research Council (NRC) requirements throughout gestation leads to maternal hyperglycemia and hyperinsulinemia. Further, newborn lambs born to OB vs control-fed (CON, 100% of NRC) ewes exhibited greater adiposity, increased blood cortisol, insulin and glucose and the elimination of the postnatal leptin spike seen in lambs born to CON ewes. This early postnatal leptin peak is necessary for the development of hypothalamic circuits, which program appetite in later life. This study evaluated the multigenerational impact of OB on insulin:glucose dynamics of mature female F1 offspring fed only to requirements throughout gestation and on their lambs (F2 generation). Design and methods: Adult F1 female offspring born to OB ( n =10) or CON ( n =7) ewes were utilized. All F1 ewes were subjected to a glucose tolerance test at midgestation and late gestation. Jugular blood was obtained from F2 lambs at birth (day 1) through postnatal day 11, and plasma glucose, insulin, cortisol and leptin concentrations were determined. Dual-energy X-ray absorptiometry was utilized to determine bone mineral density, bone mineral content, lean tissue mass and fat tissue mass. Results: Fasted blood glucose and insulin concentrations were greater ( P