Tissue-specific alterations in zinc transporter expression in intestine and liver reflect a threshold for homeostatic compensation during dietary zinc deficiency in weanling rats

Intestinal zinc (Zn) absorption and liver Zn mobilization are presumed to regulate Zn homeostasis. Several Zn transporters have been identified; however, their contribution to Zn homeostasis is poorly understood. Moreover, their regulation during periods of growth is unknown. To characterize the mechanisms that maintain Zn status, weanling rats were fed control (25 mg/kg), marginally low (MLZ; 15 mg/kg), low (LZ; 7 mg/kg), or very low (VLZ; <1 mg/kg) Zn diets for 3 wk and effects on jejunum Zip4 and ZnT1 and hepatic Zip1 and ZnT1 were assessed. Another control group was pair-fed (PF) to VLZ. The MLZ rats had lower jejunum ZnT1 protein abundance than the control. In the LZ group, we detected increased jejunum Zip4 mRNA expression and hepatic ZnT1 protein abundance and reduced jejunum Zip4 and ZnT1 and hepatic Zip1 protein abundance. VLZ had lower jejunum ZnT1 mRNA and protein abundance and hepatic Zip1 and ZnT1 protein abundance compared with the PF group. Zip4 protein was present at the intestinal villus tip in controls but was detected on the apical membrane throughout the entire villus in LZ rats. ZnT5 protein in jejunum was always detected at the apical membrane and also at the basolateral membrane of VLZ rats. In contrast, ZnT7 was found intracellularly in jejunum. Our data suggest that effects of Zn deficiency on Zn homeostasis occurs biphasically during marginal Zn deficiency through increased intestinal Zn uptake capacity and reduced intestinal Zn efflux, then during more pronounced degrees of Zn deficiency through decreased liver Zn accretion and increased hepatic Zn efflux back into circulation. These results assist in our understanding of how mammals regulate Zn homeostasis.