The significance of adipocvte-specific glycerol channel, aquaporin adipose for life-style related diseases.

脂肪细胞特异性甘油通道、水通道蛋白脂肪对生活方式相关疾病的意义。

• 批准号: 17390271
• 负责人: FUNAHASHI Touru
• 金额: $ 9.34万
• 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: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390271/
• 关键词: gene; internal medicine; cardiovascular disease; proteome; diabetes mellitus

Metabolic syndrome clusters insulin resistance, elevated blood pressure and dyslipidemia, and is a common cause of cardiovascular diseases in the world. The molecular basis of the metabolic syndrome, however, remained unclear. Accumulation of intra-abdominal adipose tissue caused by overnutrition and physical inactivity locates upstream of the metabolic syndrome. Adipose tissue had been regarded as a simple energy storage organ. Our team clarified the tissue is a huge endocrine organ to express genes for various bioactive substances, and concepualized as 'adipocytokines'. Through the study, we discovered various novel adipocyte-expressed genes. In this study, we focused adipocytokines to clarify molecular mechanism of the metabolic syndrome. Adiponectin is an adipocyte-derived protein present abundantly in plasma. Plasma level of adiponectin is decreased in subjectes with visceral fat. Blood pressure levels of adiponectin deficient mice were almost normal. When the mice were fed with h … More igh salt-diet, their blood pressure levels were elevated. The expression of endogenous nitric oxide synthetase (eNOS) and prostacyclin synthetase was augmented in the aorta of the KO mice. Adenovirus-mediated supplementation of adiponectin lowered blood pressure level of adiponectin KO mice. The effect was cancelled by the administration of L-NAME, which is a specific inhibitor of eNOS, suggesting salt-sensitive hypertension in adiponectin deficiency is caused by lack of NO and vascular endothelial cell dysfunction. A series of studies revealed that adiponectin deficiency worsened cardiac reperfusion injury, cardiac hypertrophy and vascular thrombosis. Clinical studies demonstrated that decreased plasma adiponectin (hypoadiponectinemia) is related to complexity of coronary artery lesion, coronary spasm and peripheral artery disease. Hypoadiponectinemia increased a risk of cardiovascular events in type 2 diabetic subjects and adverse cardiac events after myocardial infarction, also related to cardiovascular risks of the patients with chronic renal disease. Improvement of life-style including cessation of smoking is important to correct hypoadiponectinemia. We demonstrated blockade of adipose angiotensin receptor decreased reactive oxygen species in adipose tissue and recovered plasma adiponectin level. We also showed a novel mechanism of obesity through the analyses of the mice with lack of aquaporin 7, which we had demonstrated as a glycerol channel molecule in adipocyte. These basic and clinical studies will give an impact on the research field of the metabolic syndrome. Less

代谢综合征集胰岛素抵抗、血压升高和血脂异常于一体，是全球心血管疾病的常见病因。然而，代谢综合征的分子基础仍不清楚。由于营养过剩和缺乏体力活动而引起的腹内脂肪组织的积聚位于代谢综合征的上游。脂肪组织一直被认为是一种简单的能量储存器官。我们的团队阐明了组织是一个巨大的内分泌器官，表达各种生物活性物质的基因，并被称为“脂肪细胞因子”。通过这项研究，我们发现了许多新的脂肪细胞表达基因。本研究以脂肪细胞因子为研究对象，探讨代谢综合征的分子机制。脂联素是一种在血浆中大量存在的脂肪细胞源性蛋白质。内脏脂肪患者血浆脂联素水平降低。脂联素缺乏小鼠的血压水平几乎正常。当小鼠被喂食h ...更多信息 高盐饮食，他们的血压水平升高。内源性一氧化氮合成酶（eNOS）和前列环素合成酶在KO小鼠主动脉中的表达增强。腺病毒介导的脂联素补充降低脂联素KO小鼠的血压水平。这一作用可被eNOS特异性抑制剂L-NAME所抵消，提示脂联素缺乏时盐敏感性高血压是由NO缺乏和血管内皮细胞功能障碍引起的。一系列研究表明，脂联素缺乏可加重心脏再灌注损伤、心肌肥厚和血管血栓形成。临床研究表明，血浆脂联素水平降低（低脂联素血症）与冠状动脉病变的复杂性、冠状动脉痉挛及外周动脉疾病有关。低脂联素血症增加2型糖尿病患者心血管事件和心肌梗死后不良心脏事件的风险，也与慢性肾脏病患者的心血管风险相关。改善生活方式包括戒烟对纠正低脂联素血症很重要。我们证明阻断脂肪血管紧张素受体可降低脂肪组织中的活性氧，恢复血浆脂联素水平。我们还通过对缺乏水通道蛋白7的小鼠的分析显示了肥胖的新机制，我们已经证明了水通道蛋白7是脂肪细胞中的甘油通道分子。这些基础和临床研究将对代谢综合征的研究领域产生影响。少

项目成果

Adiponectin deficiency exacerbates lipopolysaccharide/D-galactosamine-induced liver injury in mice

• DOI: 10.3748/wjg.v12.i21.3352
• 发表时间: 2006-06-07
• 期刊: WORLD JOURNAL OF GASTROENTEROLOGY
• 影响因子: 4.3
• 作者: Matsumoto, Hitoshi;Tamura, Shinji;Hayashi, Norio
• 通讯作者: Hayashi, Norio

Pioglitazone improves left ventricular diastolic function in patients with essential hypertension

• DOI: 10.1016/j.amjhyper.2005.02.003
• 发表时间: 2005-07-01
• 期刊: AMERICAN JOURNAL OF HYPERTENSION
• 影响因子: 3.2
• 作者: Horio, T;Suzuki, M;Kawano, Y
• 通讯作者: Kawano, Y

Adiponectin levels and atherosclerotic risk factors in pediatric chronic peritoneal dialysis patients

儿童慢性腹膜透析患者脂联素水平与动脉粥样硬化危险因素

• 发表时间: 2005
• 期刊: Perit Dial Int. 25
• 作者: Bakkaloglu SA;Buyan N;Funahashi T;Pasaoglu H;Elhan AH;Hasanoglu E;Soylemezoglu O
• 通讯作者: Soylemezoglu O

Visfatin: a protein secreted by visceral fat that mimics the effects of insulin.

• DOI: 10.1097/01.ogx.0000172388.75302.e6
• 发表时间: 2005-08
• 期刊: Science
• 影响因子: 56.9
• 作者: A. Fukuhara;M. Matsuda;M. Nishizawa;Katsumori Segawa;Masaki Tanaka;Kae Kishimoto;Yasushi Matsuki

A novel index of insulin resistance determined from the homeostasis model assessment index and adiponectin levels in Japanese subjects

• DOI: 10.1016/j.diabres.2006.10.005
• 发表时间: 2007-07-01
• 期刊: DIABETES RESEARCH AND CLINICAL PRACTICE
• 影响因子: 5.1
• 作者: Matsuhisa, Munehide;Yamasaki, Yoshimitsu;Matsuzawa, Yuji
• 通讯作者: Matsuzawa, Yuji