Molecular mechanism of visceral fat syndrome, common basis of atherosclerotic diseases

内脏脂肪综合征的分子机制，动脉粥样硬化疾病的共同基础

• 批准号: 10044281
• 负责人: MATSUZAWA Yuji
• 金额: $ 3.65万
• 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-10044281/
• 关键词: obesity; visceral fat; life style-related diseases; atherosclerosis; adiponectin; 内臓脂肪症候群; 脂肪組織; Adipocytokine; Adiponectin

Obesity, defined as an overaccumulation of body fat is a basis for most common diseases, including diabetes mellitus, dyslipoproteinemia, hypertension, atherosclerotic vascular diseases, colon cancer and inflammatory bowel disease in the industrial countries. In this study, we investigated the moecular mechanisms of the life-style related diseases through the analyses of the biological properties of intra-abdomial visceral fat tissue with international collaboration.We analyzed the gene expression profile of subcutaneous and visceral adipose tissues and found that adipose tissue, especially visceral fat is not simply an energy storing organ, but is an endocrine organ expressing a variety of genes for biologically active secretory proteins. Dr. Auwerx's group in Pasteur institute in France analyzed the depot-specific expression of the genes in adipose tissues and revealed several genes predominantly expressing each adipose tissue.Through the search of adipose-expressed genes, we isolate … More d a novel cDNA abundantly specifically expressed in adipose tissue. The gene product, adiponectin was synthesized in adipose tissue and abundantly present in the circulation with the concentration of 5-10 μg/ml. Unexpectedly, plasma adiponectin levels were decreased in obesity, especially in visceral obesity. The protein suppressed adhesion of monocytes to vascular endothelial cells and proliferation of vascular smooth muscle cells in vitro, thus has a potential anti-atherogenic property. Hypoadiponectinemia observed in visceral obesity may play a role in the development of atherosclerotic vascular diseases.Dr. Auwex's group focused on PPARγ, which is a master regulator of adipocyte-differentiation and elucidated depot-specific expression of PPARγ in obesity. They also revealed that PPARγ expressed in the intestinal epithelium, and regulates the differentiation and proliferation of this cell-type. They also clarified the significance of PPARγon the development of colon cancer and Crohn's disease and the relationship between overnutrition and these diseases.We invited Dr. Auwerx in the winter meeting of Japan atherosclerotic society. Japan and France groups presented above results in the meeting. In conclsion, we progressed the studies on molecular mechanisms of diseases caused by ovemutrition by international collraboration. Less

在工业化国家，肥胖症被定义为身体脂肪的过度积累，是大多数常见疾病的基础，包括糖尿病、血脂异常、高血压、动脉粥样硬化性血管疾病、结肠癌和炎症性肠病。本研究与国际合作，通过对内脏脂肪组织生物学特性的分析，探讨了生活方式相关疾病的分子机制，分析了皮下和内脏脂肪组织的基因表达谱，发现脂肪组织，特别是内脏脂肪，不仅是一个能量储存器官，而是表达多种生物活性分泌蛋白基因的内分泌器官。法国巴斯德研究所的Auwerx博士的研究小组分析了脂肪组织中基因的储存特异性表达，发现了几个主要表达每种脂肪组织的基因。 ...更多信息 一种在脂肪组织中特异性表达的新cDNA。基因产物脂联素在脂肪组织中合成，并大量存在于循环中，浓度为5-10 μg/ml。出乎意料的是，血浆脂联素水平降低肥胖，特别是在内脏肥胖。该蛋白在体外抑制单核细胞与血管内皮细胞的粘附和血管平滑肌细胞的增殖，因此具有潜在的抗动脉粥样硬化特性。在内脏肥胖中观察到的低脂联素血症可能在动脉粥样硬化血管疾病的发展中起作用。Auwex博士的研究小组专注于PPARγ，这是脂肪细胞分化的主要调节因子，并阐明了肥胖中PPARγ的储存库特异性表达。他们还发现，PPARγ在肠上皮中表达，并调节该细胞类型的分化和增殖。他们还阐明了PPARγ在结肠癌和克罗恩病发展中的意义以及营养过剩与这些疾病的关系。我们邀请Auwerx博士参加日本动脉粥样硬化学会的冬季会议。日本和法国小组在会上介绍了上述成果。总之，通过国际合作，我们对卵巢癌致病的分子机制的研究取得了进展。少

项目成果

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