Dietary Zinc Supplementation from Organic and Inorganic Sources Induce Differential Intestinal Gene Expression in Swine

Background Zinc (Zn) is an essential mineral supplemented to animal diets from organic (bound to organic compounds) and inorganic sources (inorganic salts). Diets supplemented with organic Zn result in better animal performance than inorganic sources especially under challenges like heat stress. The mechanisms by which sources of Zn differ in their physiological effects are unknown. A study in piglets showed that organic Zn sources increase mRNA expression of Zn transporters compared to inorganic Zn. A cell line study demonstrated that amino acid‐bound Zn can be absorbed by amino acid transporters, increasing Zn bioavailability in a model of acrodermatitis enteropathica . Here, we used in vitro and in vivo models to test the hypothesis that intestinal luminal exposure to organic and inorganic Zn sources differentially affects nutrient absorption and transport in the intestine. Methods Forty‐five pigs (body weight = 77.5 ± 2.5 kg) were allocated to pens (9 pigs/pen) and randomly assigned to five different diets: a corn‐soybean meal basal diet without added Zn (control diet), or control diet supplemented with 50 ppm (low) and 100 ppm (high) of ZnCl 2 and amino acid‐bound Zn (LQ, Zinpro Corp.) as inorganic and organic sources respectively. After 32 days, ileum samples were collected and RNA was extracted for RNAseq analysis. To define if responses to Zn are due to luminal or basal signaling, mouse enteroids were microinjected with 50 ppm, 100 ppm, 150 ppm and 1000 ppm of either ZnCl 2 or LQ‐Zn to model luminal exposure or Zn sources were added to the media to identify changes induced by circulating Zn. Enteroid gene expression of relevant genes was measured by qPCR. Results Compared to control diet, ZIP4 expression was increased by high and low LQ‐Zn and high ZnCl 2 , while low ZnCl 2 induced ZIP10 expression. High ZnCl 2 diet induced expression of SLC2A6 ( GLUT6 ) compared with control. Comparison of inorganic to organic Zn sources showed 292 differentially expressed genes (DEG's) between low ZnCl 2 (n=8) and low LQ‐Zn (n=9) and 370 DEG's between high ZnCl 2 (n=8) and high LQ‐Zn (n=8). Of note, phospholipase A2 expression was repressed by high ZnCl 2 compared to high LQ‐Zn. Aminopeptidase‐N , metallothionein‐1A (MT1) , vitamin D 25‐ hydroxylase , interleukin 33 and epidermal growth factor receptor substrate 15‐like 1 genes showed higher expression induced by ZnCl 2 compared to LQ‐Zn. Enteroids luminally exposed to ZnCl 2 showed increased expression of metallothionein , Sglt1 and amino acid transporter Pept1 . Both ZnCl 2 and LQ‐Zn increased the expression of zinc transporter Zip7 in the enteroids. Zn in the enteroid media increased the expression of Glut2 , ZnT1 and Mt1 , and decreased the expression of Sglt1 , Pept1 and Zip 4 compared with no additional Zn. However, no differences were found between ZnCl 2 and LQ‐Zn treatments. Conclusions Our results suggest that Zn supplementation modulates the intestinal expression of nutrients and Zn transporters. Findings in our enteroid experiment suggest that the changes are dependent on the source of Zn only when Zn is supplemented luminally. Overall, our findings provide information on the potential mechanisms by which Zn sources can affect animal performance and health. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .