锌是一种关键的微量营养素，对于许多生理过程至关重要，包括葡萄糖代谢、炎症调节和肠道屏障功能。此外，锌代谢紊乱与慢性炎症性疾病（如2型糖尿病、肥胖症和炎症性肠病）的风险增加相关。然而，改变的锌状况是疾病发生的症状还是原因仍不清楚。这三种慢性疾病的常见症状包括肠道通透性增加和锌失衡的发生。本研究的具体重点是研究肠道通透性的膳食来源（如高蔗糖摄入）如何影响转运体介导的锌稳态和随后的与锌有关的生理过程，从而促进疾病的发展。我们使用体内亚慢性蔗糖处理、外体肠道器官培养和体外细胞系统进行研究。我们分析了锌代谢和肠道通透性的变化以及代谢结果。我们发现亚慢性蔗糖处理导致体内稳态锌分布的系统变化，并增加了65Zn的转运（从血液到肠道），同时在肠道基底膜上表达了更多ZIP14。此外，蔗糖处理增强了肠上皮细胞的存活、EGFR-AKT-STAT3通路的激活以及肠道通透性。我们的研究表明，亚慢性高蔗糖摄入改变了系统和肠道锌稳态，将膳食所致的锌稳态变化与肠道通透性和慢性疾病前驱的发生联系起来。版权所有 © 2023 Mitchell, Hung, Thorn, Zou, Baser, Gulec, Cheung and Aydemir.

Zinc is an essential micronutrient that is critical for many physiological processes, including glucose metabolism, regulation of inflammation, and intestinal barrier function. Further, zinc dysregulation is associated with an increased risk of chronic inflammatory diseases such as type II diabetes, obesity, and inflammatory bowel disease. However, whether altered zinc status is a symptom or cause of disease onset remains unclear. Common symptoms of these three chronic diseases include the onset of increased intestinal permeability and zinc dyshomeostasis. The specific focus of this work is to investigate how dietary sources of intestinal permeability, such as high sucrose consumption, impact transporter-mediated zinc homeostasis and subsequent zinc-dependent physiology contributing to disease development.We used in vivo subchronic sucrose treatment, ex vivo intestinal organoid culture, and in vitro cell systems. We analyze the alterations in zinc metabolism and intestinal permeability and metabolic outcomes.We found that subchronic sucrose treatment resulted in systemic changes in steady-state zinc distribution and increased 65Zn transport (blood-to-intestine) along with greater ZIP14 expression at the basolateral membrane of the intestine. Further, sucrose treatment enhanced cell survival of intestinal epithelial cells, activation of the EGFR-AKT-STAT3 pathway, and intestinal permeability.Our work suggests that subchronic high sucrose consumption alters systemic and intestinal zinc homeostasis linking diet-induced changes in zinc homeostasis to the intestinal permeability and onset of precursors for chronic disease.Copyright © 2023 Mitchell, Hung, Thorn, Zou, Baser, Gulec, Cheung and Aydemir.