Maternal zinc deficiency affects postnatal growth and glucose homeostasis in rat pups differently depending upon adequacy of nutrient intake

Abstract

The "thrifty" phenotype hypothesis suggests that inadequate nutrition (IN) during fetal life results in permanent metabolic modifications and increased risk of diabetes. Effects of moderate maternal zinc (Zn) deficiency on growth and glucose homeostasis in the offspring and the interaction between maternal Zn deficiency and postnatal nutrition are not well understood. Rats were fed Zn deficient (ZnD, 7 μg/g) or control diet (CON, 25 μg/g) for 3 wks, bred and kept on ZnD diet during pregnancy+lactation. Litters were culled to 7 pups/dam (AN adequate nutrition) or 13 pups/dam (IN), and another group to 3‐4 pups/dam (EN excess nutrition) at 10 d. After weaning, pups were fed rat chow, and insulin and glucose tolerance tests were done at 5 and 10 wks. Lower serum Zn and weight gain was found in ZnD‐IN than in CON‐IN pups at 20 d, but ZnD‐AN and ZnD‐EN pups weighed more than controls (+10% and +40%) with increased serum IGF‐1 in the ZnD‐AN group and increased serum glucose and insulin in the ZnD‐EN group. ZnD‐AN rats had insulin insensitivity compared to CON‐AN rats at 5 and 10 wks. At 15 wks, male ZnD‐AN rats had higher serum leptin than CON‐AN rats. Maternal Zn deficiency interacts with postnatal nutrition, resulting in divergent effects on growth and insulin resistance in the offspring. Prenatal Zn deficiency may have subsequent and potentially long term effects on glucose homeostasis through altering leptin signaling in male rats.