Luo Tian-hong, Zhao Yu, Li Guo, Zhang Hong-li, Li Wen-yi, Ldu Min
Shanghai Jiatong University Medical College, Ruijin Hospital, Shanghai Institute of Endocxrine and Metabolic Diseases, Shanghai 200025, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2007 May;23(2):229-34.
To identify genes that are differentially expressed in omental fat of normal weight subjects, obese subjects and obese type 2 diabetic patients.
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.
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 theta (YWHAZ), a negative regulator for insulin signal transduction, was up-regulated only in obese diabetic patient, but not in normal-glycemic obese subjects.
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 understanding of the pathogenesis of obesity and type 2 diabetes.
鉴定在正常体重受试者、肥胖受试者和肥胖2型糖尿病患者网膜脂肪中差异表达的基因。
使用自制的高密度cDNA微阵列,我们比较了正常体重受试者、肥胖受试者和肥胖2型糖尿病患者网膜脂肪的基因表达谱,以鉴定与肥胖和糖尿病相关的脂肪特异性基因。
肥胖患者和肥胖糖尿病患者中分别有119个和257个基因上调,而肥胖患者和肥胖糖尿病患者中分别有46个和58个基因下调。77个基因,包括代谢相关基因(PDK4)、小窝蛋白2、金属硫蛋白1B,在肥胖和肥胖糖尿病患者中均上调,而8个基因,包括脂质合成中的关键酶,如HMG-CoA合酶、脂肪酸合酶和硬脂酰-CoA去饱和酶,在两组中均下调。另一个有趣的发现是,酪氨酸-3-单加氧酶/色氨酸5-单加氧酶激活蛋白θ(YWHAZ),一种胰岛素信号转导的负调节因子,仅在肥胖糖尿病患者中上调,而在血糖正常的肥胖受试者中未上调。
我们的研究表明,脂肪组织中脂肪生成的减少以及脂肪酸氧化的增加可能是肥胖和2型糖尿病中胰岛素抵抗的共同原因,而其他基因的功能变化,如免疫调节基因,也可能参与肥胖和2型糖尿病的发病机制。胰岛素信号转导的阻断可能触发从肥胖到糖尿病的转变。对这些基因的进一步探索将极大地帮助我们理解肥胖和2型糖尿病的发病机制。