Clarification of molecular mechanism in anti-atherogenic action of an adipocytedrived matrix protein, adiponectin.

阐明脂肪细胞驱动的基质蛋白脂联素抗动脉粥样硬化作用的分子机制。

• 批准号: 11671086
• 负责人: NAKAMURA Tadashi
• 金额: $ 1.98万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671086/
• 关键词: adiponectin; obesity; type 2 diabetes; atherosclerosis; vascular endothelial cell; adohesion molecule; TNF-α; NFκB; 脂肪細胞; 冠動脈疾患; 糖尿病

We identified a novel adipocyte-derived matrix protein, adiponectin, which is abundantly present in the circulation. We showed that obese subjects and subjects with coroary artery disease (CAD) exhibited decreased plasma concentrations of adiponectin and also, in vitro study, that this protein suppressed the attachment of monocytes to endothelial cells through the decreased expression of adhesion molecules such as ICAM-1, VCAM-1, and E-selectin, which is an early event in atherosclerotic vascular change.In the present study, we observed the relationship between plasma adiponectin concentrations and disorders susceptible to atherosclerosis including type 2 diabetes, and aiso clarified the molecular mechanism in its anti-atherogenic actions.We confirmed that plasma adiponectin cncentrations were decreased in many obese subjects and the subjects with CAD.Furthermore, we observed plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in age- and BMI-matched non-diabetic subjects. The plasma adiponectin concentrations of diabetic patients with CAD were lower than those of diabetic patients without CAD.Weight reduction significantly elevated plasma adiponectin levels in both the diabetic and the non-diabetic subjects.We previously observed that adiponectin inhibited tumor necrosis factor-α (TNF-α)-induced expression of endothelial adhesion molecules. In the current study, we demonstrated that adiponectin specifically supressed TNF-α-induced IκB-α-NFκB activation through a cAMP -dependent pathway in human aortic endothelial cells.

我们发现了一种新的脂肪细胞来源的基质蛋白，脂联素，这是大量存在于循环。我们发现肥胖受试者和冠状动脉疾病（CAD）受试者表现出脂联素的血浆浓度降低，并且在体外研究中，这种蛋白质通过降低粘附分子如ICAM-1、VCAM-1和E-选择素的表达来抑制单核细胞与内皮细胞的粘附，这是动脉粥样硬化血管变化的早期事件。我们观察了血浆脂联素浓度与动脉粥样硬化易感性疾病（包括2型糖尿病）的关系，并阐明了脂联素抗动脉粥样硬化作用的分子机制。我们证实，许多肥胖者和CAD患者血浆脂联素浓度降低。此外，我们观察到无CAD的糖尿病患者的脂联素血浆水平低于年龄和BMI匹配的非糖尿病患者。合并CAD的糖尿病患者的血浆脂联素浓度低于未合并CAD的糖尿病患者。体重减轻可显着升高糖尿病和非糖尿病受试者的血浆脂联素水平。我们之前观察到脂联素抑制肿瘤坏死因子-α（TNF-α）诱导的内皮粘附分子的表达。在本研究中，我们证实脂联素通过cAMP依赖性途径特异性抑制TNF-α诱导的人主动脉内皮细胞IκB-α-NFκB活化。

项目成果

Hotta K.,Nakamura T.,Funahashi T.et al.: "Mutation in bombesin receptor subtype-3 gene is not a major cause of obesity in the Japanese"Horm. Metab. Res.. (in press). (2000)

Hotta K.、Nakamura T.、Funahashi T.等人：“铃蟾肽受体亚型 3 基因突变并不是日本人肥胖的主要原因”Horm.

Ouchi N.,Kihara S.,Nakamura T.,Funahashi T.et al.: "Novel modulator for endotherial adhesion molecules: adipocyte-derived plasma protein, adiponectin"Circulation. 100(25). 2473-2476 (1999)

Ouchi N.，Kihara S.，Nakamura T.，Funahashi T.等人：“内皮粘附分子的新型调节剂：脂肪细胞衍生的血浆蛋白，脂联素”循环。

T.Yoshizumi, et al: "Abdominal fat : standeardized technique for measurement at CT"Radiology. 211. 283-286 (1999)

T.Yoshizumi 等人：“腹部脂肪：CT 测量的标准化技术”放射学。

Takahashi M.,Funahashi T.et al.: "Genomic structure and mutations in adipose-specific gene, adiponectin"Int. J. Obes.. (in press). (2000)

Takahashi M.，Funahashi T.et al.：“脂肪特异性基因脂联素的基因组结构和突变”Int。

Y.Arita, et al: "Paradoxical decrease of anadipose-specific protein, adiponectin, in obesity."Biochem.Biophys.Res.Commun. 257. 79-83 (1999)

Y.Arita 等人：“肥胖症中脂肪特异性蛋白脂联素的反常减少。”Biochem.Biophys.Res.Commun。