Identification of adipose-specific genes and teir clinical significance

脂肪特异性基因的鉴定及其临床意义

• 批准号: 10557101
• 负责人: MATSUZAWA Yuji
• 金额: $ 8万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10557101/
• 关键词: obesity; visceral fat; life style-related diseases; atherosclerosis

Accumulation of excess body fat has become a common basis for the development of non-insulin dependent diabetes mellitus (NIDDM) and atherosclerotic vascular diseases (AVD). Body fat distribution is a independent r the risk for above diseases. Deposition of intra-abdominal viscreal fat rather than subcutaneous fat closely relates to the development of NIDDM and AVD. The aim of this study is to clarify the biological difference between subcutaneous and visceral fat tissues and to apply the data to clinical medicine.By the comparison of the gene expression profiles of subcutaneous and visceral fat tissues, subcutaneous fat has been revealed predominantly to express "static" genes for the proteins maintaining fundamental cellular functions including ribosomal protein and cytoskeleton proteins. On the other hand, visceral fat predominantly expressed the genes for a variety of secretory proteins with biological activities.We focused on two genes, that is, adiponectin, which was obtained by … More a large-scale-random sequencing of adipose-tissue cDNA library and clone 085, which was isolated by diferential display technique. Adiponectin is plasma protein specifically produced and secreted from adipose tisuue. Plasma levels of adiponectin, however, decreased in the obese subjects, especially those with visceral fat accumulation. Marked reduction of plasma adiponectin concentration was observed in he patients with coronary artey disease compaired with BMI-matched conrols. Therefore, decreased plasma adponectin has been proven to be a potential risk for coronary artery disease. The proein showed anti-atherogenic properties, including suppresion of monocyte-adhesion to endothelial cells and proliferation of vascular diseases.The product of clone 085 belonged to hematopoietic factors The expression of mRNA for clone 085 increased in visceral fat during the development of obesity. Plasma levels of clone 085 products increased in paralel with the amount of visceral fat in mice. In humans, plasma 085 level was closely correlated with the amount of visceral fat but not with subcutaneous fat.In this study, we investigated in the visceral fat derived factors. The measurement of plasma levels of these visceral fat derived factors will be a clue for understanding the pathogenesis of diseases accompanied by visceral fat obesity. Less

体内脂肪的过量积累已成为非胰岛素依赖型糖尿病（NIDDM）和动脉粥样硬化性血管疾病（AVD）发展的共同基础。体脂分布与上述疾病的发病风险无关。NIDDM和AVD的发生与腹腔内可见脂肪的沉积密切相关，而与皮下脂肪的沉积无关。通过比较皮下脂肪和内脏脂肪组织基因表达谱，发现皮下脂肪主要表达维持细胞基本功能的核糖体蛋白和细胞骨架蛋白等“静态”基因，从而阐明皮下脂肪和内脏脂肪组织的生物学差异，并为临床应用提供依据。另一方面，内脏脂肪主要表达多种具有生物活性的分泌蛋白的基因。 ...更多信息 对脂肪组织cDNA文库和差异显示技术分离的克隆085进行大规模随机测序。脂联素是脂肪组织特异性产生和分泌的血浆蛋白。然而，肥胖者血浆脂联素水平下降，尤其是内脏脂肪堆积者。冠心病患者血浆脂联素水平明显低于BMI匹配的对照组。因此，血浆脂联素降低已被证明是冠状动脉疾病的潜在风险。蛋白质具有抗动脉粥样硬化的作用，包括抑制单核细胞与内皮细胞的粘附和血管疾病的增殖，克隆085的产物属于造血因子，克隆085的mRNA在内脏脂肪中的表达随着肥胖的发展而增加。克隆085产物的血浆水平随着小鼠内脏脂肪量的增加而增加。在人类中，血浆085水平与内脏脂肪量密切相关，但与皮下脂肪量无关。测定这些内脏脂肪源性因子的血浆水平将为了解内脏脂肪性肥胖相关疾病的发病机制提供线索。少

项目成果

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