Key Laboratory of Aquaculture Nutrition and Feed, Ministry of Agriculture & Key Laboratory of Mariculture, Ministry of Education, College of Fisheries, Ocean University of China, Qingdao, China.
State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, China.
J Nutr Biochem. 2024 Jan;123:109473. doi: 10.1016/j.jnutbio.2023.109473. Epub 2023 Oct 14.
Vitamin D (VD) is a steroid hormone that is widely known to play an important role in maintaining mineral homeostasis, and regulating various physiological functions. Our previous results demonstrated that the interruption of VD metabolism caused hyperglycemia in zebrafish. In the present study we further explored the mechanism that VD regulates glucose metabolism by maintaining intestinal homeostasis in zebrafish. Our results showed that the expression of several peptide hormones including gastric inhibitory peptide, peptide YY, and fibroblast growth factor 19 in the intestine decreased, while the expression of sodium glucose cotransporter-1 and gcg was increased in the intestine of the zebrafish fed with the VD-deficient diet. Consistently, similar results were obtained in cyp2r1 zebrafish, in which endogenous VD metabolism is blocked. Furthermore, the results obtained from germ-free zebrafish exhibited that VD-regulated glucose metabolism was partly dependent on the microbiota in zebrafish. Importantly, the transplantation of gut microbiota collected from cyp2r1 zebrafish to germ-free zebrafish led to hyperglycemic symptoms in the fish, which were associated with the altered structure and functions of the microbiota in cyp2r1 zebrafish. Interestingly, the treatments with acetate or Cetobacterium somerae, a potent acetate producer, lowered the glucose contents whereas augmented insulin expression in zebrafish larvae. Notably, acetate supplementation alleviated hyperglycemia in cyp2r1 zebrafish and other diabetic zebrafish. In conclusion, our study has demonstrated that VD modulates the gut microbiota-SCFAs-gastrointestinal hormone axis, contributing to the maintenance of glucose homeostasis.
维生素 D（VD）是一种甾体激素，广泛参与维持矿物质稳态和调节各种生理功能。我们先前的研究结果表明，VD 代谢中断会导致斑马鱼发生高血糖。在本研究中，我们进一步探讨了 VD 通过维持肠道内稳态来调节葡萄糖代谢的机制。研究结果表明，在喂食缺乏 VD 饮食的斑马鱼肠道中，几种肽类激素（包括胃抑制肽、肽 YY 和成纤维细胞生长因子 19）的表达下调，而肠道中钠-葡萄糖协同转运蛋白-1 和 gcg 的表达增加。在 Cyp2r1 斑马鱼中也获得了相似的结果，因为 Cyp2r1 阻断了内源性 VD 代谢。此外，无菌斑马鱼的研究结果表明，VD 调节的葡萄糖代谢部分依赖于斑马鱼的肠道微生物群。重要的是，从 Cyp2r1 斑马鱼中收集的肠道微生物群移植到无菌斑马鱼中，导致鱼发生高血糖症状，这与 Cyp2r1 斑马鱼中微生物群的结构和功能改变有关。有趣的是，用乙酸或 Cetobacterium somerae（一种有效的乙酸产生菌）处理可降低葡萄糖含量，同时增加斑马鱼幼虫的胰岛素表达。值得注意的是，乙酸补充可缓解 Cyp2r1 斑马鱼和其他糖尿病斑马鱼的高血糖症状。总之，我们的研究表明，VD 调节肠道微生物群-短链脂肪酸-胃肠激素轴，有助于维持葡萄糖稳态。
