肥胖及2型糖尿病患者内脏脂肪基因差异表达研究  

IDENTIFICATION OF GENES THAT ARE DIFFERENTIALLY EXPRESSED IN OMENTAL FAT OF NORMAL WEIGHT SUBJECTS, OBESE SUBJECTS AND OBESE DIABETIC PATIENTS

作　　者：骆天红[1] 赵萸[1] 李果[1] 张宏利[1] 李文毅[1] 罗敏[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院,上海市内分泌代谢病研究所,上海200025

出　　处：《中国应用生理学杂志》2007年第2期229-234,共6页Chinese Journal of Applied Physiology

基　　金：国家科技攻关项目(2002BA711A05);国家自然科学基金资助项目(30100084);全国博士论文作者专项资金(200360);上海市启明星计划资助项目(03QC14040)

摘　　要：目的筛查在正常人、单纯性肥胖患者及肥胖伴2型糖尿病患者内脏脂肪组织中差异表达的基因。方法利用自制的高密度cDNA芯片,比较正常人、单纯性肥胖患者及肥胖伴2型糖尿病患者内脏脂肪组织中差异表达的基因,以寻找脂肪组织特异的与肥胖及糖尿病发生有关的基因。结果和正常人相比,在肥胖患者及肥胖伴2型糖尿病患者中上调的基因分别有119个和257个,下调的基因分别有46和58个。这些基因中有77个在两组中均上调,其中包括与代谢有关的基因,如丙酮酸脱氢酶激酶4(PDK4)以及窖蛋白、金属硫因蛋白等;8个基因在两组中均下调,其中包括脂肪合成途径中的关键酶,如3-羟基-3-甲基戊二酸单酰辅酶A(HMG-CoA)合成酶、脂肪酸合成酶及硬脂酰辅酶A脱氢酶。另外,酪氨酸-3-单加氧酶-色氨酸-5-单加氧酶活化蛋白θ(YWHAZ)仅在肥胖伴2型糖尿病患者中上调,而在单纯性肥胖患者中不变,该基因所编码的蛋白在胰岛素信号转导途径中起着负调控的作用。结论脂肪组织中脂肪生成下降、脂肪酸氧化增加可能是肥胖及2型糖尿病中胰岛素抵抗发生的共同原因,其它基因功能的改变也可能参与了肥胖及2型糖尿病的发生,而胰岛素信号转导受阻可能是肥胖向糖尿病转化的促进因素。对这些基因的进一步研究将有助于更好地了解肥胖及糖尿病的发生机制。To identify genes that are differentially expressed in omental fat of normal weight subjects, obese subjects and obese type 2 diabetic patients. Methods： Using a home-made high-density cDNA microarray, we compared gene expression profile of omental fat from normal weigh subjects, obese subjects and obese type 2 diabetic patients, to identify adipose-specific genes associated with obesity and diabetes. Results： 119 and 257 genes were up-regulated in obese patients and obese diabetic patients respectively, while 46 and 58 genes were down-regulated in obese patients and obese diabetic patients respectively. 77 genes, including metabolism related genes （PDK4）, and caveolin 2, metallo thionein 1B, were up-regulated in both obese and obese diabetic patients, while 8 genes, including key enzymes in lipid synthesis, such as HMG-CoA synthase, fatty acid synthase and stearoyl-CoA desaturase, were down-regulated in both groups. Another interesting finding was that tyrosine-3-monooxygenase/ tryptophan 5-monooxygenase activation protein θ（YWHAZ）, a negative regulator for insulin signal transduction, was up-regulated only in obese diabetic patient, but not in normal- glycemic obese subjects. Conclusion： Our study demonstrated that decrease of lipogenesis along with increase of fatty acids oxidation of adipose tissue could be a common cause of insulin resistance in obesity and type 2 diabetes, while functional changes of other genes, such as immune regulation genes, might also be involved in the pathogenesis of obesity and type 2 diabetes. Block of insulin signal transduction might trigger the transition from obesity to diabetes. Further exploration of these genes will greatly help us in the under-standing of the pathogenesis of obesity and type 2 diabetes.

关 键 词：肥胖 糖尿病 芯片 脂肪组织 

分 类 号：R587[医药卫生—内分泌]