High Sucrose Diet Induces Intestinal Zinc Dyshomeostasis and Permeability

OBJECTIVES: Zinc (Zn) is an essential micronutrient that is critical for many physiological processes including glucose metabolism, regulation of inflammation, regulation of intestinal barrier function, and insulin production and secretion. Further, Zn dysregulation is associated with increased risk of chronic inflammatory diseases such as type II diabetes, inflammatory bowel disease, and obesity. However, it remains unclear whether altered Zn status is a symptom or cause of disease onset. Common symptoms of these three inflammatory diseases include the onset of intestinal inflammation and increased intestinal permeability. The specific focus of this work is to investigate how dietary sources of chronic inflammation, such as high sucrose consumption impacts transporter mediated Zn homeostasis and subsequent Zn dependent physiology. METHODS: To study the interactions between high dietary sucrose and Zn homeostasis, we administered 30% sucrose water to mice for 8 weeks. Tissue metal contents were measured by microwave plasma atomic emission spectrometry. Zn transport was measured using radioisotope tracing of (65)Zn. Intestine permeability was assessed by FITC-dextran (4 kDa) assay. Protein expression of Zn transporters, inflammatory markers, and tight junction proteins was measured by western blot. RESULTS: Sucrose treatment resulted in systemic changes in steady-state Zn distribution, including a significant increase in plasma Zn and significant decreases in Zn in the liver, pancreas, and white adipose tissue. We observed changes in Zn transport protein expression in the intestine. In agreement with altered transporter expression, Zn transport studies revealed significant dysregulation of Zn transport in both the small intestine and colon. Further, sucrose treatment resulted in induction of both P-STAT3 and P-NF-κB, dysregulation of tight junction proteins ZO-1 and CLDN1, and increased intestine permeability. CONCLUSIONS: Our work suggests that chronic high sucrose consumption leads to changes in systemic Zn homeostasis. This links diet-induced changes in Zn homeostasis to the onset of precursors of chronic disease, intestinal inflammation and permeability. FUNDING SOURCES: This work was supported by Cornell University Division of Nutritional Sciences funds to T. B. Aydemir.