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老年小鼠糖耐量减退与脂肪细胞分化关系的实验研究
武晓慧,杨蕙宇,王轲,宁晓霞,黄振鹏,李蓉,徐玉乔
0
(西安医学院临床医学院;空军军医大学第一附属医院病理科)
摘要:
【摘要】 目的 研究老年小鼠糖耐量减退与脂肪细胞分化的关系,为探索老年性糖尿病的发病机制提供基础依据。方法 取6、20、40周龄C57BL/6J小鼠,分别模拟人类的青少年期,中年期和老年期,检测体重、附睾白色脂肪重量/体重、空腹血糖、葡萄糖耐量以及冷暴露后体温,取小鼠背部棕色脂肪及附睾、皮下、腹股沟和肠系膜脂肪进行组织学分析。采用RTqPCR方法检测各组小鼠肝脏、腓肠肌以及附睾、皮下、腹股沟和肠系膜脂肪的葡萄糖转运蛋白4(GLUT4,小鼠称为Slc2a4)基因相对表达量。在背部棕色脂肪及附睾、皮下、腹股沟和肠系膜5个部位的脂肪组织检测Ucp1、Prdm16和Cidea基因并在后4个部位的脂肪组织检测CD137和Cytc基因的mRNA相对表达量。采用Western Blot法检测小鼠棕色脂肪解偶联蛋白1(Ucp1)的表达。对棕色脂肪及皮下、腹股沟区脂肪组织的Ucp1相对表达量与各年龄组空腹血糖做相关分析。结果 40周龄小鼠体重、附睾脂肪重量/体重及空腹血糖水平明显高于6周龄组(均P<005),并存在糖耐量减退(P<005);各部位脂肪组织中Slc2a4基因表达均呈下降趋势(P<005)。棕色脂肪细胞脂滴增大并融合,细胞标志物Ucp1、Prdm16和Cidea基因表达量(P<005)及Ucp1的蛋白表达量均下降,40周龄组小鼠在4℃环境下体温下降更快(P<005)。小鼠附睾白色脂肪细胞直径随年龄增长逐渐增大,皮下、腹股沟和肠系膜区域米色脂肪分化逐渐减少。米色脂肪分子标志物Ucp1、Prdm16、Cidea、CD137、CytC出现不同程度的表达下调(P<005)。20周龄组小鼠的以上部分指标也出现不同程度的改变。背部棕色脂肪及皮下和腹股沟区脂肪的Ucp1基因表达量均与空腹血糖呈负相关(R2=0974;R2=08933;R2=07109)。结论 老年小鼠棕色脂肪形态和功能减退以及米色脂肪细胞分化减少与其糖耐量减退密切相关。
关键词:  老年  糖耐量减退  棕色脂肪  米色脂肪  Ucp1
DOI:
基金项目:国家自然科学基金(31400722);陕西省教育厅科研项目(17JK0654)
Study about the relationship between impaired glucose tolerance and Adipocytes’ differentiation in aged mice
WU Xiaohui,YANG Huiyu,WANG Ke,NING Xiaoxia,HUANG Zhenpeng,LI Rong,XU Yuqiao
(School of Clinical Medicine, Xian Medical University;Department of Pathology, The First Affiliate Hospital of Air Force Medical University)
Abstract:
【Abstract】 Objective To study the changes of adipocyte differentiation in the pathogenesis of senile diabetes mellitus (ADM) or glucose intolerance and explore the pathogenesis of ADM. Methods C57BL/6J mice of 6 weeks, 20 weeks and 40 weeks age were used to simulate the youth, middle age and old age humans, respectively. The body weight, epididymal fat weight/body weight, fasting blood glucose, glucose tolerance and body temperatures after cold exposure were measured. The brown adipose Tissue (BAT) in the interscapular region of the mice and the epididymal, subcutaneous, inguinal and mesenteric adipose tissue were analyzed. Realtime RTqPCR was used to detect relative mRNA expression of glucose transporter 4 (GlUT4, it’s Slc2a4(solute carrier family 2 (facilitated glucose transporter), member 4) in mice) in liver, gastrocnemius muscle, and in epididymal, subcutaneous, inguinal and mesenteric adipose tissues. The relative mRNA expressions of Ucp1, Prdm16 and Cidea genes were detected in BAT and epididymal, subcutaneous, inguinal and mesenteric adipose tissue, and CD137 and Cytc genes were detected in the last four sites. Expression of Ucp1 in BAT of mice was detected by Western Blot. Correlation analysis was done between relative mRNA expression of Ucp1 in BAT, subcutaneous and inguinal adipose tissues and fasting blood glucose in mice. Results The body weight, epididymal fat weight/body weight and fasting blood glucose level of 40weekold mice are significantly greater or higher than those of 6weekold mice (P<005), and 40weekold mice have impaired glucose tolerance(P<005). The expression of Slc2a4 gene in all parts of adipose tissues was down regulated (P<005). The lipid droplet size of brown adipocytes increased and they fused, the gene expression of Ucp1, Prdm16 and Cidea (P<005) and the Ucp1 protein decreased. The body temperature of 40weekold mice dropped more rapidly at 4 ℃ environment (P<005). The white adipocyte size in the epididymal adipose tissue increased with age, and the differentiation of beige adipocytes in subcutaneous, inguinal and mesenteric adipose tissue decreased gradually and the expression of Ucp1, Prdm16, Cidea, CD137 and CytC decreased with age (P<005). Some indicators of 20weekold mice were also changed. The expression of Ucp1 gene in BAT, subcutaneous and inguinal adipose tissues were negatively correlated with fasting blood glucose(R2=0974;R2=08933;R2=07109). Conclusion Deterioration in morphology and function of brown adipocytes and the decrease of beige adipocyte differentiation are closely related to impaired glucose tolerance in aged mice.
Key words:  Old age  Impaired glucose tolerance  Brown adipocytes  Beige adipocytes  Ucp1

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