The Effects of Short-Term Zinc Feeding on Zinc Absorption and Zinc Transporter Expression in the Small Intestine of Mice

Abstract

Abstract Objectives Zinc homeostasis is primarily maintained by zinc transporters that regulate zinc uptake and efflux in the small intestine; however, no study to date has comprehensively examined zinc transporter expression in the small intestine of mice fed varying levels of dietary zinc. The objective of this study was to determine the effects of zinc absorption and zinc transporter expression in the small intestine of mice fed varying levels of zinc for one week. Methods Seven-week-old male C57BL/6 J mice were randomized to either a standard AIN-93 G diet containing 30 ppm zinc (zinc adequate) or modified AIN-93 G diets containing <1 ppm (zinc deficient) or 100 ppm zinc (zinc supplemented) for one week (n = 5–10/diet). Mice were given an oral gavage containing a slurry of zinc deficient feed and 10 μg 67 Zn; plasma isotope appearance was determined 6-h later by ICP-MS. Gene expression of Slc39a1–14 and Slc30a1–10 was determined in each intestinal segment (duodenum, jejunum, and ileum) by RT-qPCR. Results Plasma and liver zinc concentrations were not different after one week of feeding (P > 0.05 for both). Plasma appearance of 67 Zn was greater in mice fed the zinc deficient (mean ± SD: 0.36 ± 0.03 ng/mL) compared to the zinc adequate (0.22 ± 0.03 ng/mL) and zinc supplemented (0.22 ± 0.03 ng/mL, P < 0.0001 for both) diets. With the exception of Slc39a12, Slc30a3, and Slc30a8, the remaining zinc transporters were expressed across all diets and intestinal segments. Expression of Slc39a1, Slc39a4, Slc39a5, Slc39a7, Slc39a9, Slc39a11, Slc39a14, Slc30a2, Slc30a4, Slc30a5, Slc30a6, and Slc30a9 changed with diet (Pdiet < 0.05 for all); expression of Slc39a3, Slc39a7, Slc39a9 and Slc30a5 changed by intestinal segment (Psegment < 0.05 for all). Of those transporters expressed, Slc39a4 was positively associated with plasma appearance of 67 Zn (r = 0.645, P < 0.0001) and increased 7-fold in mice consuming the zinc deficient diet compared to the zinc adequate and zinc supplemented diets (P < 0.0001 for both). Conclusions Although most zinc transporters are expressed in the small intestine and likely function in concert, fluctuations in fractional zinc absorption are positively correlated with Slc39a4 expression in the small intestine. Funding Sources The views expressed herein are those of the authors and do not reflect official policy of the Army, DoD, or US Government. Supported by MRDC.