Regulatory responses to excess zinc ingestion in growing rats.

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The growth of weaning piglets is effectively improved by feeding a high-Zn diet (3000 mg Zn/kg of diet). The present study examined whether feeding a diet supplemented with Zn (1016-3000 mg/kg) for 10 d induces growth benefits in rats. In addition, tissue weight, Zn content of tissues and expression of Zn transporters were examined in these rats. Zn supplementation did not significantly increase body weight. Breaking line model analyses indicated that the weight of the pancreas, the organ most sensitive to excess Zn, significantly decreased with increasing Zn intake beyond 15·2 mg/d. Excess Zn has been suggested to accumulate in the liver, kidney and bone in order to protect the pancreas. Zn concentrations in the plasma, liver, kidney and femur increased with increasing Zn intake up to approximately 30 mg/d, whereas those in the pancreas increased up to 8·4 mg/d and decreased by Zn intake beyond 8·4 mg/d. The expression levels of the Zn transporters Zip4 and ZnT1 in the intestinal epithelium were significantly lower in rats fed a diet supplemented with 1016 mg/kg Zn compared to those fed the basal diet. The present study reveals that (1) excess Zn intake does not accelerate growth in rats, but is detrimental to the pancreas, (2) the excess Zn is effectively accumulated in the liver, kidney and bone, without sufficient protection of the pancreas and (3) expression of Zn transporters is down-regulated in response to excess Zn intake.