Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
Department of Health Sciences, Università del Piemonte Orientale, Novara, Italy.
J Steroid Biochem Mol Biol. 2018 Sep;182:37-49. doi: 10.1016/j.jsbmb.2018.04.009. Epub 2018 Apr 21.
Vitamin D (VD) deficiency (VDD) correlates to obesity, with VD a recognized mediator of metabolic diseases. From a previous proteomic study identifying adiponectin as a link between VDD and pediatric obesity, herein we analysed another protein (SSP2301) increased with VDD. A focused 2D-electrophoretic analysis identified 4 corresponding plasma proteins, with one predicted to be fetuin B (FETUB). FETUB was studied due to its emerging role in metabolic diseases and cytogenetic location (3q27.3) with adiponectin. Results were confirmed in obese children, where plasma FETUB was higher with VDD. A direct effect by 1α,25-(OH)2D3 on hepatocellular FETUB synthesis was observed, with a time and dose dependent reduction. Further, we demonstrated the VD-receptor (VDR) is key, with FETUB "released" with VDR silencing. Finally, VD supplementation (6weeks) to juvenile mice fed a standard diet, reduced plasma FETUB. Only at 22weeks did liver FETUB correspond to plasma FETUB, highlighting the contribution of other VD-responsive tissues. Overall, FETUB is a key protein linking VDD to pediatric obesity. With an emerging role in metabolic diseases, we demonstrate that VD/VDR directly regulate FETUB.
维生素 D（VD）缺乏症（VDD）与肥胖相关，VD 是代谢性疾病的公认介质。从之前的蛋白质组学研究中发现脂联素是 VDD 与儿科肥胖之间的联系，在此我们分析了另一种与 VDD 相关的蛋白质（SSP2301）。一项集中的 2D 电泳分析鉴定出 4 种相应的血浆蛋白，其中一种预测为胎球蛋白 B（FETUB）。由于 FETUB 在代谢性疾病和细胞遗传学位置（3q27.3）与脂联素的关系，因此研究了 FETUB。在肥胖儿童中得到了证实，VDD 时血浆 FETUB 升高。观察到 1α，25-（OH）2D3 对肝细胞 FETUB 合成的直接影响，呈时间和剂量依赖性降低。此外，我们证明了维生素 D 受体（VDR）是关键，VDR 沉默会导致 FETUB“释放”。最后，用标准饮食喂养的幼年小鼠补充维生素 D（6 周），降低了血浆 FETUB。只有在 22 周时，肝脏 FETUB 才与血浆 FETUB 相对应，突出了其他对维生素 D 有反应的组织的贡献。总之，FETUB 是将 VDD 与儿科肥胖联系起来的关键蛋白。由于其在代谢性疾病中的作用不断增加，我们证明了 VD/VDR 直接调节 FETUB。
