摘要
目的探讨维生素D3对高脂饲料诱导的小鼠脂肪组织内质网应激以及胰岛素抵抗的影响。方法雄性C57BL/6小鼠80只，分为对照组（20只）和实验组（60只），分别给予普通饲料和高脂饲料喂养。肥胖模型构建成功之后，将实验组小鼠分为单纯高脂喂养组（HFD）、维生素D3常规剂量（50 IU/kg）喂养组（VitD-L）以及维生素D3大剂量（250 IU/kg）喂养组（VitD-H），喂养1周。取内脏脂肪组织，采用Western印迹法检测脂肪组织内质网应激关键基因免疫球蛋白重链结合蛋白（Bip）、磷酸化肌醇需求激酶1（p-IRE1）、磷酸化类PKR的内质网激酶（p-PERK）及核转录因子NF-κB蛋白表达量；取外周血测定肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、血清25-羟基维生素D、空腹血糖、HbA1C、三酰甘油和空腹胰岛素水平，并计算胰岛素抵抗指数。结果维生素D3喂养可以下调内质网应激关键基因Bip、p-IRE1、p-PERK的表达，同时降低核转录因子NF-κB蛋白表达以及炎症因子TNF-α和IL-6的水平（均P〈0.05）；同时可以明显降低肥胖小鼠的空腹血糖、HbA1C、三酰甘油和空腹胰岛素水平（均P〈0.05），且能明显改善肥胖小鼠的胰岛素抵抗。结论维生素D3可以明显改善高脂饲料诱导的肥胖小鼠炎症反应及胰岛素抵抗的发生，这种作用的发挥可能通过抑制脂肪组织内质网应激实现。
Objective To study the effect of vitamin D3 on adipose tissue endoplasmic reticulum stress and insulin resistance induced by high fat diet in mice.Methods Eighty male C57BL/6 mice were divided into control group（n=20）and experimental group（n=60）, fed with common food and high fat diet, respectively. After the establishment of the obesity model, the experimental mice were divided into control group, low-dose（50 IU/kg）vitamin D3 group（VitD-L）, and high-dose（250 IU/kg）vitamin D3 group（VitD-H）. After the mice were fed for 1 week, Western blot was used to detect the expressions of immunoglobulin heavy chain-binding protein（Bip）, phosphorylated inositol-requiring enzyme 1（p-IRE1）, phosphorylated protein kinase R（PKR）-like endoplasmic reticulum kinase（p-PERK）, and NF-κB protein in adipose tissue. Serum levels of TNF-α, IL-6, serum 25-hydroxyvitamin D, fasting plasma glucose, HbA1C, triacylglyceride, and fasting insulin were measured and the insulin resistance index was calculated.Results Vitamin D3 down-regulated the expressions of endoplasmic reticulum stress key genes including Bip, p-IRE1, and p-PERK; and decreased the protein expression of NF-κB and the serum levels of TNF-α and IL-6（P〈0.05）. Vitamin D3 also significantly reduced the levels of fasting blood glucose, HbA1C, triacylglyceride, and fasting insulin in obese mice（P〈0.05）, while alleviated the insluin resistance in obese mice.Conclusion Vitamin D3 may significantly improve inflammatory response and insulin resistance via inhibiting endoplasmic reticulum stress in adipose tissue of obese mice.
出处
《中华内分泌代谢杂志》
CAS
CSCD
北大核心
2017年第10期861-864,共4页
Chinese Journal of Endocrinology and Metabolism
基金
上海浦东卫生与计划生育委员会人才开发项目（PWRd2014-16）,上海卫生与计划生育委员会（201540126）,浦东新区科委科技发展基金项目（PKJ2014-Y18）
关键词
肥胖
维生素D3
内质网应激
胰岛素抵抗
Obesity
Vitamin D3
Endoptasmic reticulum stress
Insulin resistance
作者简介
通信作者：李晓华，Email：xiaohua_li16@163．com
