Roles of adipose tissue in survival, differentiation and lipotoxicity of cardiomyocytes

脂肪组织在心肌细胞存活、分化和脂毒性中的作用

• 批准号: 23591050
• 负责人: TODA Shuji
• 金额: $ 3.33万
• 依托单位: Saga University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591050/
• 关键词: 脂肪組織; 心筋細胞; 脂肪毒性; メタボリックシンドローム; 脂肪滴沈着; 心不全; アポトーシス; 遊離脂肪酸; 肥満; 心外膜下脂肪組織; 内臓脂肪組織; 皮下脂肪組織

This research has shown that epicardial, subcutaneous and visceral adipose tissue types promote lipid droplet deposition and apoptosis of cardiomyocytes together with the inhibition of the growth and differentiation. That is, 3 adipose tissue types above promote lipotoxicity of cardiomyocytes. Our results support the clinical finding that obesity is closely associated with heart failure. Also, our study has demonstrated that the free fatty acid palmitate, fatty acid transport proteins of FATP-4 and CD34, and oxidative molecules of 8-OHdG and 4-HNE may be involved in the lipotoxicity of cardiomyocytes. In addition, this research has shown that cardiomyocytes inhibit the development of preadipocytes and mesenchymal stem cells, and the production of cardiomyocyte-toxic adipokine of leptin from adipose tissue. That is, cardiomyocytes themselves protect against the adipose tissue-driven lipotoxicity.

本研究表明，心外膜、皮下和内脏脂肪组织类型促进心肌细胞脂滴沉积和凋亡，抑制心肌细胞生长分化。即以上3种脂肪组织类型均促进心肌细胞的脂肪毒性。我们的研究结果支持了肥胖与心力衰竭密切相关的临床发现。此外，我们的研究表明，游离脂肪酸棕榈酸酯、脂肪酸转运蛋白FATP-4和CD34以及8-OHdG和4-HNE的氧化分子可能参与了心肌细胞的脂肪毒性。此外，本研究表明，心肌细胞抑制脂肪前体细胞和间充质干细胞的发育，并抑制脂肪组织产生心肌细胞毒性脂肪因子瘦素。也就是说，心肌细胞本身可以防止脂肪组织驱动的脂肪毒性。

项目成果

Three-dimensional culture model for analyzing crosstalk between adipose tissue and hepatocytes.

用于分析脂肪组织和肝细胞之间串扰的三维培养模型。

• 发表时间: 2013
• 期刊: Cell Tissue Res
• 影响因子: 3.6
• 作者: Nishijima-Matsunobu A;Aoki S;Uchihashi K;Fujimoto K;Toda S
• 通讯作者: Toda S

Adipose tissue behavior is distinctly regulated by neighboring cells and fluid flow stress: a possible role of adipose tissue in peritoneal fibrosis

• DOI: 10.1007/s10047-013-0702-8
• 发表时间: 2013-03
• 期刊: Journal of Artificial Organs
• 影响因子: 1.3
• 作者: S. Aoki;Kazuma Udo;H. Morimoto;Satoshi Ikeda;T. Takezawa;K. Uchihashi;Aki Nishijima‐Matsunobu;M. Noguchi;H. Sugihara;S. Toda

Establishment of a long-term three-dimensional primary culture of mouse glandular stomach epithelial cells within the stem cell niche.

• DOI: 10.1016/j.bbrc.2013.02.051
• 发表时间: 2013-03-22
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Katano, Takahito;Ootani, Akifumi;Joh, Takashi
• 通讯作者: Joh, Takashi

A Promising Culture Model for Analyzing the Interaction between Adipose Tissue and Cardiomyocytes

• DOI: 10.1210/en.2010-1106
• 发表时间: 2011-04-01
• 期刊: ENDOCRINOLOGY
• 影响因子: 4.8
• 作者: Anan, Mayumi;Uchihashi, Kazuyoshi;Toda, Shuji
• 通讯作者: Toda, Shuji

Epithelial-to-mesenchymal transition and slit function of mesothelial cells are regulated by the cross talk between mesothelial cells and endothelial cells

• DOI: 10.1152/ajprenal.00543.2013
• 发表时间: 2014-01-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
• 影响因子: 4.2
• 作者: Aoki, Shigehisa;Takezawa, Toshiaki;Toda, Shuji
• 通讯作者: Toda, Shuji