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首页> 外文期刊>BMC Medical Genomics >Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes
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Gene expression profiling of subcutaneous adipose tissue in morbid obesity using a focused microarray: Distinct expression of cell-cycle- and differentiation-related genes

机译：使用聚焦微阵列对病态肥胖者皮下脂肪组织的基因表达谱分析：细胞周期和分化相关基因的不同表达

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Background Obesity results from an imbalance between food intake and energy expenditure, which leads to an excess of adipose tissue. The excess of adipose tissue and adipocyte dysfunction associated with obesity are linked to the abnormal regulation of adipogenesis. The objective of this study was to analyze the expression profile of cell-cycle- and lipid-metabolism-related genes of adipose tissue in morbid obesity. Methods We used a custom-made focused cDNA microarray to determine the adipose tissue mRNA expression profile. Gene expression of subcutaneous abdominal fat samples from 15 morbidly obese women was compared with subcutaneous fat samples from 10 nonobese control patients. The findings were validated in an independent population of 31 obese women and 9 obese men and in an animal model of obesity (Lepob/ob mice) by real-time RT-PCR. Results Microarray analysis revealed that transcription factors that regulate the first stages of adipocyte differentiation, such as CCAAT/enhancer binding protein beta (C/EBPβ) and JUN, were upregulated in the adipose tissues of morbidly obese patients. The expression of peroxisome proliferator-activated receptor gamma (PPARγ), a transcription factor which controls lipid metabolism and the final steps of preadipocyte conversion into mature adipocytes, was downregulated. The expression of three cyclin-dependent kinase inhibitors that regulate clonal expansion and postmitotic growth arrest during adipocyte differentiation was also altered in obese subjects: p18 and p27 were downregulated, and p21 was upregulated. Angiopoietin-like 4 (ANGPTL4), which regulates angiogenesis, lipid and glucose metabolism and it is know to increase dramatically in the early stages of adipocyte differentiation, was upregulated. The expression of C/EBPβ, p18, p21, JUN, and ANGPTL4 presented similar alterations in subcutaneous adipose tissue of Lepob/ob mice. Conclusions Our microarray gene profiling study revealed that the expression of genes involved in adipogenesis is profoundly altered in the subcutaneous adipose tissue of morbidly obese subjects. This expression pattern is consistent with an immature adipocyte phenotype that could reflect the expansion of the adipose tissue during obesity.
机译：背景技术肥胖症是由于食物摄入和能量消耗之间的不平衡而导致的，脂肪组织过多。与肥胖相关的过多的脂肪组织和脂肪细胞功能障碍与脂肪生成的异常调节有关。这项研究的目的是分析病态肥胖中脂肪组织的细胞周期和脂质代谢相关基因的表达谱。方法我们使用定制的聚焦cDNA微阵列确定脂肪组织mRNA表达谱。将来自15位病态肥胖妇女的皮下腹部脂肪样本的基因表达与来自10位非肥胖对照患者的皮下脂肪样本进行了比较。通过实时RT-PCR，在31名肥胖妇女和9名肥胖男性的独立人群和肥胖动物模型（Lep ob / ob 小鼠）中证实了这一发现。结果微阵列分析显示，在肥胖的病态肥胖患者的脂肪组织中，调控脂肪细胞分化初期的转录因子，例如CCAAT /增强子结合蛋白β（C /EBPβ）和JUN，被上调。降低了过氧化物酶体增殖物激活受体γ（PPARγ）的表达，PPARγ是一种控制脂质代谢和将脂肪前细胞转化为成熟脂肪细胞的最终步骤的转录因子。在肥胖受试者中，三种调节细胞增殖期间克隆扩增和有丝分裂后生长停滞的细胞周期蛋白依赖性激酶抑制剂的表达也发生了改变：p18和p27被下调，p21被上调。上调类血管生成素样4（ANGPTL4），它调节血管生成，脂质和葡萄糖代谢，并且已知在脂肪细胞分化的早期阶段急剧增加。 C /EBPβ，p18，p21，JUN和ANGPTL4的表达在Lep ob / ob 小鼠皮下脂肪组织中表达相似。结论我们的微阵列基因分析研究表明，在肥胖病患者皮下脂肪组织中，参与脂肪形成的基因表达发生了深刻的改变。该表达模式与未成熟的脂肪细胞表型一致，该表型可以反映肥胖期间脂肪组织的膨胀。

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