Pregnancy and lactation have anti-obesity and anti-diabetic effects in A(y)/a mice

Dominant 'yellow' mutation at the mouse agouti locus (A(y)) results in obesity. Pregnancy and lactation are characterized by large energy demand. The aim of this study was to investigate whether obesity would develop in pregnant and suckling A(y) mice. Body weight and food intake in pregnancy, lactation, and after weaning, plasma leptin, insulin, corticosterone and blood glucose concentrations on days 7, 13 and 18 of pregnancy, days 1, 10, 21 and 80 postpartum, glucose and insulin tolerance on pregnancy days 7 and 18 were measured in C57Bl/6J mice of a/a (normal metabolism) and A(y)/a genotypes. The same parameters were also measured in age-matched virgin females. Virgin A(y)/a females exhibited hyperphagia, enhanced body weight, glucose intolerance and normal blood parameters at the mating age. With age, they developed obesity, hyperleptinaemia, hyperinsulinaemia and hyperglycaemia. Obesity did not develop in mated A(y)/a mice; during suckling, they had equal food intake and body weight as a/a mice. During pregnancy, glucose tolerance was enhanced in A(y)/a mice and became equal in both genotypes. In both genotypes, concentrations of hormones increased, and glucose decreased from pregnancy day 7 to day 18 and returned to normal values after parturition. A(y)/a mice did not differ from a/a in corticosterone, insulin and glucose levels during pregnancy and lactation, in leptin levels during suckling; however, A(y)/a mice had two times higher leptin levels than a/a during pregnancy. After weaning, A(y)/a mice began to eat and weigh more than a/a exhibiting normal metabolic parameters for 50 days. Pregnancy and lactation retard obesity and diabetes development in A(y) mice.