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

肥胖，被定义为身体脂肪的过度积累，是大多数常见疾病的基础，包括工业化国家的糖尿病、脂蛋白异常血症、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，通过分析腹腔内内脏脂肪组织的生物学特性，探讨生活方式相关疾病的分子机制。我们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仅是一个简单的能量储存器官，而是一个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，发现了几种主要表达每种脂肪组织的基因。通过对脂肪表达基因的搜索，我们分离出了一种新的在脂肪组织中特异表达的cDNA。基因产物脂联素在脂肪组织中合成，在循环中大量存在，浓度为5 ~ 10 μg/ml。出乎意料的是，肥胖患者血浆脂联素水平下降，尤其是内脏型肥胖患者。该蛋白在体外抑制单核细胞对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。在内脏性肥胖中观察到的低脂联素血症可能在动脉粥样硬化性血管疾病的发展中起作用。Auwex的研究小组专注于PPARγ，它是脂肪细胞分化的主要调节因子，并阐明了PPARγ在肥胖中的储存特异性表达。他们还发现PPARγ在肠上皮中表达，并调节这种细胞类型的分化和增殖。他们还阐明了ppar γ在结肠癌和克罗恩病发生发展中的意义以及营养过剩与这些疾病的关系。我们邀请了Auwerx博士参加日本动脉粥样硬化学会的冬季会议。日本和法国集团在会议上提出了上述结果。总之，通过国际合作，我们在营养过剩引起疾病的分子机制研究方面取得了进展。少

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