The significance of adipocyte-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: 17590930
• 负责人: NAKAMURA Tadashi
• 金额: $ 2.24万
• 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: 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/en/grant/KAKENHI-PROJECT-17590930/
• 关键词: aquaporin; glycerol; adipocyte; life-style related disease; glycerol kinase; Foxo 1; IRE-1; knockout mouse; 肥満; IRE1; インスリン抵抗性

In the present study, we investigated the relationship between AQPap and obesity in mice lacking AQPap. There is no difference in body weight of WT and KO mice, but KO mice become obese after 12 weeks of age. Adipose tissue weights of AQPap KO mice are significantly heavier than WT mice at 20 weeks of age. Histlogical analysis shows an increase in hypertrophic adipocytes in WAT of KO mice. KO mice exhibit whole body insulin resistance associated with obesity. We also demonstrated that knock down of AQPap in 3T3-L1 adipocytes increases intracellular glycerol contents, elevates glycerol kinase activities, enhances oleic acid uptake, and finally results in TG accumulation (PNAS 2005).Furthermore, we investigated the effect of AQP ap on the differentiation of adipocytes. The stromal vascular cells (SVCs) which are isolated from WAT of WT or AQPap KO mice are differentiated to adipocytes and the adipocytes after 2,4 and 6 days from induction are examined the staining by oil red O and the genetic expression of PPAR. There are no differences between SVC adipocytes derived from WT and KO mice. The medium concentration of glycerol is significantly lower in SVC adipocytes from KO mice than in those from WT mice during the lipolytic state induced by epinephrine. These findings suggest that AQPap is a glycerol channel without the effects on the differentiation of adipocytes. We could also identify a fork-head type transcriptional factor, Foxol, as one of the promoters for AQPap using 3T3-L1 adipocytes or 293 cells and confirm the Foxo 1 binds insulin response element (IRE) 1 site by gel shift assay.Our series of these results were presented in News ＆ Views of Nature 2005 and moreover, we published the review for AQPap and glycerol metabolism in BBA 2006.

在本研究中，我们在缺乏 AQPap 的小鼠中研究了 AQPap 与肥胖之间的关系。 WT和KO小鼠的体重没有差异，但KO小鼠在12周龄后变得肥胖。 20周龄时AQPap KO小鼠的脂肪组织重量明显重于WT小鼠。组织学分析显示 KO 小鼠 WAT 中肥大脂肪细胞增加。 KO 小鼠表现出与肥胖相关的全身胰岛素抵抗。我们还证明，敲低 3T3-L1 脂肪细胞中的 AQPap 会增加细胞内甘油含量，提高甘油激酶活性，增强油酸摄取，最终导致 TG 积累 (PNAS 2005)。此外，我们研究了 AQP ap 对脂肪细胞分化的影响。从WT或AQPap KO小鼠的WAT中分离的基质血管细胞(SVC)分化为脂肪细胞，并且在诱导2,4和6天后检查脂肪细胞的油红O染色和PPAR的基因表达。 WT 和 KO 小鼠的 SVC 脂肪细胞之间没有差异。在肾上腺素诱导的脂肪分解状态下，KO 小鼠的 SVC 脂肪细胞中甘油的中等浓度显着低于 WT 小鼠的脂肪细胞。这些发现表明，AQPap 是一种甘油通道，对脂肪细胞的分化没有影响。我们还可以使用3T3-L1脂肪细胞或293细胞鉴定出叉头型转录因子Foxol作为AQPap的启动子之一，并通过凝胶转移实验确认Foxo 1结合胰岛素反应元件（IRE）1位点。我们的一系列结果发表在News & Views of Nature 2005上，此外，我们还在BBA 2006上发表了AQPap和甘油代谢的综述。

项目成果

Diagnostic Criteria for Metabolic Syndrome in Japan and Its Clinical Significance.

日本代谢综合征的诊断标准及其临床意义。

• 发表时间: 2007
• 期刊: Int Med (in press)
• 作者: Nakamura T;et al.
• 通讯作者: et al.

Aquaporins and glycerol metabolism

• DOI: 10.1016/j.bbamem.2006.01.008
• 发表时间: 2006-08-01
• 期刊: BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
• 影响因子: 3.4
• 作者: Hibuse, Toshiyuki;Maeda, Norikazu;Funahashi, Tohru
• 通讯作者: Funahashi, Tohru

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

Adiponectin replenishment ameliorates obesity-related hypertension

• DOI: 10.1161/01.hyp.0000222368.43759.a1
• 发表时间: 2006-06-01
• 期刊: HYPERTENSION
• 影响因子: 8.3
• 作者: Ohashi, Koji;Kihara, Shinji;Shimomura, Iichiro
• 通讯作者: Shimomura, Iichiro

Blockade of angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation

• DOI: 10.1038/sj.ki.5001810
• 发表时间: 2006-11-01
• 期刊: KIDNEY INTERNATIONAL
• 影响因子: 19.6
• 作者: Kurata, A.;Nishizawa, H.;Funahashi, T.
• 通讯作者: Funahashi, T.