Pathophysiological Role of Adipocyte Expressed Genes in Common Disease

脂肪细胞表达基因在常见疾病中的病理生理作用

基本信息

批准号：
15081208
负责人：
KIHARA Shinji
金额：
$ 73.73万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15081208/
关键词：
GENE INTERNAL MEDICINE CARDIOVASCULAR HYPERTENSION DIABETES MELLITUS PROTEOME 内臓脂肪 C-reactive protein 血管新生

项目摘要

Metabolic syndrome is the common cause of atherosclerotic cardiovascular diseases. We have reported that visceral fat accumulation is the key feature of thepathophysiology, and found adiponectin and aquaporin adipose from human adipose tissue cDNA library.Plasma adiponectin levels positively correlated to insulin sensitivity and endothelium-dependent vasodilation, and negatively correlated with visceral fat mass. Hypoadiponectinemia was an independent risk for type 2 diabetes, hypertension and coronary artery disease. Moreover, the subjects with genetic hypoadiponectinemia had high susceptibility to the metabolic syndrome. The adiponectin deficient mice exhibited diet-induced diabetes mellitus or hypertension, pressure overload-stimulated adverse cardiac hypertrophy, ischemia-reperfusion injury-induced increased myocardial infarct size, and glomerular hyperfiltration-induced exacerbation of urinary albumin and renal fibrosis. Adiponectin supplementation restored these abnormalities, in … More dicating that adiponectin insufficiency involves obesity-linked diabetes, hypertension, kidney disease, and cardiovascular diseases. In cultures of vascular endothelial cells and cardiac myocytes, adiponectin augmented AMP-activated protein kinase and suppressed the cell death. In cultures of macrophages, adiponectin treatment suppressed foam cell transformation, and increased tissue inhibitor of metalloproteinase-1 levels through enhanced interleukin-10 secretion. These findings suggest that adiponectin protect systemic vascular system from adverse nutritional, inflammatory, and mechanical stress overload. In addition, we investigated the role of aquaporin adipose, the glycerol channel in adipocyte. Aquaporin adipose-deficient mice showed a disrupted increase of plasma glycerol and rapid reduction of plasma glucose during prolonged fasting. The fat mass and adipocyte size were increased significantly in aquaporin adipose-deficient mice compared with control mice. Aquaporin adipose disruption caused the enhanced glycerol kinase enzymatic activity in adipocytes. These findings suggest that aquaporin adipose dysfunction causes hypoglycemia, accelerated adipose triglycerides synthesis, and, finally, develops obesity.The measurement of plasma adiponectin level will be clinically useful to evaluate diabetic and atherosclerotic disease risk. The adipocyte expressed genes including adiponectin and aquaporin adipose can be target molecules for preventing life style-mediated metabolic and cardiovascular diseases. Less

代谢综合征是动脉粥样硬化心血管疾病的常见原因。我们已经报道说，内脏脂肪的积累是病理生理学的关键特征，并从人脂肪组织cDNA库中发现了脂联素和水白通道蛋白脂肪。铂脂联素水平与胰岛素敏感性和依赖性血管降低和依赖性血管降低，并与脂肪呈负相关。低脂肪膜内血症是2型糖尿病，高血压和冠状动脉疾病的独立风险。此外，患有遗传性低脂肪核血症的受试者对代谢综合征具有很高的敏感性。脂联素缺乏小鼠暴露于饮食诱发的糖尿病或高血压，压力过载的不良心脏肥大，缺血 - 再灌注损伤诱导的增加的心肌感染的大小增加以及肾小球过滤过滤诱导的尿中白蛋白和肾脏纤维纤维的恶化。脂联素补充剂恢复了这些异常，在……更辨别脂联素的功能不全涉及肥胖连接的糖尿病，高血压，肾脏疾病和心血管疾病。在血管内皮细胞和心肌细胞的培养物中，脂联素增强了AMP激活的蛋白激酶，并抑制了细胞死亡。在巨噬细胞的培养物中，脂联素治疗抑制了泡沫细胞的转化，并通过增强的白介素-10分泌来抑制金属蛋白酶-1水平的组织抑制剂。这些发现表明，脂联素保护全身性血管系统免受不良营养，炎症和机械胁迫超负荷的影响。此外，我们研究了脂肪细胞中甘油通道水通道蛋白脂肪的作用。水通道蛋白脂肪缺陷小鼠在长时间禁食期间的血浆甘油含量有所破坏，血浆甘氨酸的迅速减少。与对照小鼠相比，在缺乏脂肪的小鼠中，脂肪质量和脂肪细胞的大小显着增加。水通道蛋白脂肪破坏导致脂肪细胞中增强的甘油激酶活性。这些发现表明，水通道蛋白脂肪功能障碍会导致低血糖症，加速脂肪甘油酸酯的合成，最后发展肥胖。血浆脂联蛋白水平的测量将在临床上有用，以评估糖尿病患者和动脉粥样硬化疾病风险。脂肪细胞表达的基因在内，包括脂联素和水通道蛋白脂肪可能是预防生命式介导的代谢和心血管疾病的靶标分子。较少的

项目成果

期刊论文数量（151）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Clinical significance of high-molecular weight form of adiponectin in male patients with coronary artery disease.

DOI：
10.1253/circj.72.508
发表时间：
2008
期刊：
Circulation journal : official journal of the Japanese Circulation Society
影响因子：
0
作者：
N. Komura;S. Kihara;Mina Sonoda;M. Kumada;Koichi Fujita;A. Hiuge;T. Okada;Yasuhiko Nakagawa
通讯作者：
N. Komura;S. Kihara;Mina Sonoda;M. Kumada;Koichi Fujita;A. Hiuge;T. Okada;Yasuhiko Nakagawa

Adiponectin as a Molecular Link between inflammation and Atherosclerosis

脂联素作为炎症和动脉粥样硬化之间的分子联系

DOI：
发表时间：
2004
期刊：
影响因子：
0
作者：
井福正隆;他;Kihara S
通讯作者：
Kihara S

アディポサイトカインと心血管病

脂肪细胞因子与心血管疾病

DOI：
发表时间：
2021
期刊：
影响因子：
0
作者：
増田真志;山本浩範;竹谷豊;桑原頌治，八幡大希，外池奈実，雜賀果南，木越菜々恵，安澤俊紀，辰巳佐和子;倉澤茂樹，丹葉寬之，立山清美，木村大介，岩永竜一郎;Akio Ikeda;大内乗有　大橋浩二　室原豊明
通讯作者：
大内乗有　大橋浩二　室原豊明

Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue