摘要
目的探究胰高血糖素样肽1(glucagon-like peptide 1,GLP-1)通过类血管生成因子4(angiopoietin-like protein 4,ANGPTL4)参与棕色脂肪(brown adipose tissue,BAT)功能的调节。方法小鼠分组后皮下埋泵干预6周,取材前进行葡萄糖耐量试验及pet-CT,取空腹血、棕色脂肪及肝脏进行胆固醇和三酰甘油定量、FPLC、qPCR、Western blotting、转录组测序等实验。结果GLP-1类似物Exendin-4(Ex-4)改善糖尿病db/db小鼠糖耐量异常,降低外周血和BAT中三酰甘油浓度。Ex-4促进棕色组织UCP-1表达,pet-CT提示活性增加。Ex-4促进BAT中ANGPTL4的表达,ANGPTL4缺失降低了BAT活性。结论GLP-1促进BAT活性伴有ANGPTL4表达水平的升高,ANGPTL4的缺失降低了BAT活性和功能,可能成为BAT活性调控的治疗靶点。
Objective To explore glucagon-like peptide 1(GLP-1)whether and how to regulate the function of brown adipose tissue(BAT)though angiopoietin-like protein 4(ANGPTL4).Methods Mice were randomized and controlled to receive subcutaneous pump intervention for 6 weeks.Before sampling,glucose tolerance test and pet-CT were conducted.Fasting blood,brown fat and liver were taken for cholesterol and triglyceride quantification,FPLC,qPCR,Western blotting,and transcriptometric sequencing,etc.Results GLP-1 analogue exendin-4(Ex-4)improved abnormal glucose tolerance in diabetic db/db mice and reduced triglyceride levels in peripheral blood and BAT.Ex-4 promoted the expression of UCP-1 in BAT,and pet-CT indicated increased activity;Ex-4 promotes the expression of ANGPTL4 in BAT;the deletion of ANGPTL4 decreased the activity of BAT.Conclusion GLP-1 promoted BAT activity accompanied by increased expression level of ANGPTL4,and the deficiency of ANGPTL4 lowered the activity and function of BAT,which may become a therapeutic target for the regulation of BAT activity.
作者
颜岑
罗小敏
冯英梅
Yan Cen;Luo Xiaomin;Feng Yingmei(Central Laboratory, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China)
出处
《首都医科大学学报》
CAS
北大核心
2020年第2期217-224,共8页
Journal of Capital Medical University
基金
国家自然科学基金(81470566,81670765)。
关键词
胰高血糖素样肽1
类血管生成因子4
棕色脂肪
活性
2型糖尿病
glucagon-like peptide 1
angiopoietin-like protein 4
brown adipose tissue
activity
type 2 diabetes mellitus
