Objectives: Dominant "yellow" mutation at the mouse agouti locus (Ay) affects the central regulation of energy homeostasis via disturbance of the melanocortin signalling pathway.It increases food intake and results in obesity in mice.Pregnancy and lactation are associated with changes in energy balance due to a dramatic increase in energy demand.The Ay mutation influence on appetite and metabolism during pregnancy and lactation is unknown.The work aim was to study carbohydrate metabolism and hypothalamic regulation of appetite in pregnant and suckling Aymice.Methods: Body weight, food intake, and hypothalamic NPY and AgRP expression in pregnancy, lactation, and after weaning, plasma leptin, insulin, corticosterone and blood glucose concentrations on days 7, 13, 18 of pregnancy, days 1, 10, 21, 80 postpartum, glucose and insulin tolerance on pregnancy days 7, 18 and after weaning were measured in C57Bl/6J mice ofa/a (normal metabolism) and Ay/a genotypes.The same parameters were also measured in agematched virgin females.Results: Virgin Ay/a as compared to a/a females exhibited enhanced food intake and body weight, decreased glucose tolerance and insulin sensitivity, decreased AgRP and the same NPY expression, and the same blood parameters at the mating age.With age, they developed obesity, hyperleptinemia, hyperinsulinemia, and hyperglycemia.Obesity and diabetes did not develop in mated Ay/a mice.During pregnancy, they improved their glucose tolerance and retained this improvement after weaning.Pregnant Ay/a as compared to a/a mice had higher food intake in the first and lower in the second half of pregnancy, higher leptin levels and lower NPY and AgRP expression.Suckling Ay/a mice had equal food intake, body weight, blood parameters and NPY and AgRP expression as a/a mice.After weaning, Ay/a mothers began to eat and to weigh more than their a/a counterparts but exhibited normal metabolic parameters for 50 days.Conclusion: Pregnancy and lactation improve metabolism and retard obesity and diabetes development in Ay-mice.The absence ofAy mutation influence on food intake regulation and metabolism in lactating mice suggests that melanocortin-independent signalling predominates in the regulation of energy balance during lactation.