PDF(Pubmed)
Abstract：
Vitamin D3 (VD3) is a steroid hormone that plays pivotal roles in pathophysiology, and 1,25(OH)2D3 is the most active form of VD3. In the current study, the crucial role of VD3 in maintaining energy homeostasis under short-term fasting conditions was investigated. Our results confirmed that glucose-depriving pathways were inhibited while glucose-producing pathways were strengthened in zebrafish after fasting for 24 or 48 h. Moreover, VD3 anabolism in zebrafish was significantly suppressed in a time-dependent manner under short-fasting conditions. After fasting for 24 or 48 h, zebrafish fed with VD3 displayed a higher gluconeogenesis level and lower glycolysis level in the liver, and the serum glucose was maintained at higher levels, compared to those fed without VD3. Additionally, VD3 augmented the expression of fatty acids (FAs) transporter cd36 and lipogenesis in the liver, while enhancing lipolysis in the dorsal muscle. Similar results were obtained in cyp2r1-/- zebrafish, in which VD3 metabolism is obstructed. Importantly, it was observed that VD3 induced the production of gut GLP-1, which is considered to possess a potent gluconeogenic function in zebrafish. Meanwhile, the gene expression of proprotein convertase subtilisin/kexin type 1 (pcsk1), a GLP-1 processing enzyme, was also induced in the intestine of short-term fasted zebrafish. Notably, gut microbiota and its metabolite acetate were involved in VD3-regulated pcsk1 expression and GLP-1 production under short-term fasting conditions. In summary, our study demonstrated that VD3 regulated GLP-1 production in zebrafish by influencing gut microbiota and its metabolite, contributing to energy homeostasis and ameliorating hypoglycemia under short-term fasting conditions.
摘要：
维生素D3（VD3）是一种类固醇激素，在病理生理学中起着关键作用，和1,25(OH)2D3是VD3的最活性形式。在目前的研究中,研究了VD3在短期禁食条件下维持能量稳态的关键作用.我们的结果证实，禁食24或48h后，斑马鱼的葡萄糖剥夺途径受到抑制，而葡萄糖产生途径得到加强。在短期禁食条件下，斑马鱼的VD3合成代谢以时间依赖性方式受到显着抑制。禁食24或48小时后，用VD3喂养的斑马鱼在肝脏中表现出更高的糖异生水平和更低的糖酵解水平，血清葡萄糖维持在较高水平，与没有VD3的喂食相比。此外,VD3增强脂肪酸（FAs）转运体cd36的表达和肝脏中的脂肪生成，同时增强背侧肌肉的脂解作用。在cyp2r1-/-斑马鱼中获得了类似的结果，其中VD3代谢受阻。重要的是,观察到VD3诱导肠道GLP-1的产生,其被认为在斑马鱼中具有有效的糖异生功能。同时,前蛋白转化酶枯草杆菌蛋白酶/kexin1型（pcsk1）的基因表达，GLP-1加工酶，在短期禁食斑马鱼的肠道中也被诱导。值得注意的是,在短期禁食条件下，肠道微生物群及其代谢物乙酸盐参与VD3调节的pcsk1表达和GLP-1产生。总之,我们的研究表明，VD3通过影响肠道菌群及其代谢产物来调节斑马鱼GLP-1的产生，有助于能量稳态和改善短期禁食条件下的低血糖。
