Maternal Zinc Deficiency in Rats Affects Growth and Glucose Metabolism in the Offspring by Inducing Insulin Resistance Postnatally ,

Abstract

Interactions among zinc (Zn), insulin, and glucose metabolism are complex. Maternal Zn deficiency affects maternal carbohydrate metabolism, but the mechanisms underlying changes in glucose homeostasis of offspring are not well understood. Rats consumed Zn-deficient (ZnD; 7 microg/g) or control (ZnC; 25 microg/g) diets ad libitum from 3 wk preconception to 21 d postparturition. Litters were culled to 7 pups/dam postnatally and pups were allowed to nurse their original mothers; after weaning, pups were fed nonpurified diet. Insulin and glucose tolerance tests were performed on the pups at wk 5 and 10. Although there was no difference in birth weight between groups, ZnD pups weighed significantly more than controls by d 10 (+5%) and 20 (+10%). Both blood glucose and serum insulin-like growth factor (IGF-1) concentrations at wk 3 were significantly higher in ZnD pups than in controls. Both male and female ZnD rats were less sensitive to insulin and glucose stimulation than controls at wk 5 and 10. At wk 15, serum leptin concentrations were higher in male ZnD rats than in controls. Phosphorylation of muscle Akt protein, an insulin receptor (IR) signaling intermediate, was lower in female ZnD rats than in controls at wk 15, but they did not differ in phosphorylation of IR. Maternal Zn deficiency resulted in greater serum IGF-1 concentrations and the excessive postnatal weight gain in their offspring as well as impaired subsequent glucose sensitivity. It was associated with gender-specific alterations in the serum leptin concentration and the insulin signaling pathway. These findings suggest that suboptimal maternal Zn status induces long-term changes in the offspring related to abnormal glucose tolerance.

Maternal zinc restriction affects postnatal growth and glucose homeostasis in rat offspring differently depending upon adequacy of their nutrient intake

“…Sex-specific effects of maternal Zn restriction on insulin signaling cascades (decreased Akt phosphorylation) in skeletal muscle of female offspring were demonstrated in our previous study (18), and similar effects on liver insulin signaling in female offspring with adequate postnatal nutrition (AN group) were observed in this study. Furthermore, maternal Zn restriction was associated with the depression of hepatic insulin signaling in both male and female offspring in the postnatally overfed group (EN group), suggesting that the combination of maternal Zn restriction and excess available calories/nutrients postnatally may impair downstream insulin signaling.…”

“…The potentially large number of vulnerable pregnant women with mild Zn restriction worldwide is difficult to estimate but may be a reason for an increase in the development of insulin resistance. In a previous study using a rat model, we observed that maternal Zn restriction caused impaired glucose sensitivity in the offspring (18). However, effects of differences in postnatal nutrition and interactions between maternal Zn restriction and postnatal nutritional manipulations on the offspring were not investigated.…”

Gene-Environment Interactions Controlling Energy and Glucose Homeostasis and the Developmental Origins of Obesity

“…A number of studies in animal models have also investigated the effects of micronutrient deficiency in the offspring. Maternal zinc deficiency in rats has been associated with increased leptin levels, insulin resistance, and impaired glucose tolerance in the offspring (233). Similar observations were observed in a rat model of maternal dietary chromium restriction (384).…”

Maternal Mortality in India: An Overview of social causes

“…Zinc Deficiency, wide spread in the developing country has been associated with long labour, increases the risk for maternal deaths (King, 2000;Jou, 2010). Several studies across the world have shown that zinc supplementation helps in reducing the complications during pregnancy (Chaffee, 2012;UNICEF, 2014).…”