Clinical application of Nesfatin-1 to obesity from the point of the suppression of adipogenesis.

Nesfatin-1从抑制脂肪生成角度治疗肥胖症的临床应用

• 批准号: 20590247
• 负责人: OKADA Shuichi
• 金额: $ 3.08万
• 依托单位: Gunma University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590247/
• 关键词: 肥満; 脂肪分化; 脂肪細胞分化; Nucleobindin-2; 生理活性; シグナル伝達; 生体分子; 細胞・組織; 動物; 摂食; ホルモン

Nucleobindin-2 is a 396 amino acid EF-hand Ca^<2+> binding protein that can be further processed to generate an 82 amino terminal peptide termed Nesfatin-1. To examine the function of Nucleobindin-2 in adipocyte differentiation, culutred 3T3-L1 adipogenesis were incubated with various concentrations of GST, GST-Nucleobindin-2, GST-DNesfatin-1 or GST-Nesfatin-1 prior to and during the initiation of adipocyte differentiation. Nucleobindin-2 treatment at physiological concentrations decreased neutral lipid accumulation (Oil-Red O staining) and expression of several marker genes for adipocyte differentiation (PPAR・, aP2, and adipsin). In contrast, deletion of the Nesfatin-1 domain in Nucleobindin-2 (DNesfatin-1) had no significant effect on 3T3-L1 adipocyte differentiation. Although Nesfatin-1 treatment alone also reduced 3T3-L1 adipocyte differentiation and expression of marker genes, this required super physiologic concentrations. Moreover, 3T3-L1 cells stably over expresseing Nuclobindin-2 displayed a significant reduction of adipocyte differentiation. In contrast, reduced expression of Nucleobindin-2 by shRNA resulted in a marked increase of adipocyte differentiation. Taken together, these data indicate that Nucleobindin-2 is secreted from preadipocytes and functions as a suppressor of adipocyte differentiation.

nucleobinin -2是一个396个氨基酸的EF-hand Ca^<2+>结合蛋白，可以进一步加工生成一个82个氨基酸的末端肽，称为Nesfatin-1。为了研究核结合蛋白-2在脂肪细胞分化中的作用，在脂肪细胞分化开始前和开始过程中，用不同浓度的GST、GST-核结合蛋白-2、GST- dnesfatin -1或GST- nesfatin -1孵育培养的3T3-L1脂肪细胞。生理浓度的核结合素-2处理降低了中性脂质积累（油红O染色）和脂肪细胞分化的几个标记基因（PPAR·、aP2和adipsin）的表达。相反，核结合蛋白-2 （DNesfatin-1）中Nesfatin-1结构域的缺失对3T3-L1脂肪细胞的分化没有显著影响。虽然Nesfatin-1单独治疗也会降低3T3-L1脂肪细胞的分化和标记基因的表达，但这需要超生理浓度。此外，稳定过表达nuclobinin -2的3T3-L1细胞显示出脂肪细胞分化的显著减少。相反，shRNA表达核结合蛋白-2的减少导致脂肪细胞分化明显增加。综上所述，这些数据表明，核联蛋白-2是由前脂肪细胞分泌的，并作为脂肪细胞分化的抑制因子。

项目成果

Carbohydrate response element binding protein(ChREBP)gene expression is positively regulated by thyroid hormone

碳水化合物反应元件结合蛋白（ChREBP）基因表达受甲状腺激素正向调节

• 发表时间: 2009
• 期刊: Endocrinology 150
• 作者: Koshi Hashimoto;Emi Ishida;Shunichi Matsumoto;Shuichi Okada;Masanobu Yamada;TetsuroSatoh;Tsuyoshi Monden;Masatomo Mori
• 通讯作者: Masatomo Mori

Nesfatin/Nesfatin-1はadipogenesisを抑制する

Nesfatin/Nesfatin-1 抑制脂肪生成

• 发表时间: 2009
• 作者: 三浦敦子;岡田秀一等
• 通讯作者: 岡田秀一等

Fasting concentrations of nesfatin-1 are negatively correlated with body mass index in non-obese males

• DOI: 10.1111/j.1365-2265.2010.03835.x
• 发表时间: 2010-10-01
• 期刊: CLINICAL ENDOCRINOLOGY
• 影响因子: 3.2
• 作者: Tsuchiya, Takafumi;Shimizu, Hiroyuki;Mori, Masatomo
• 通讯作者: Mori, Masatomo

Administration time difference of Candesartin effect on albuminuria in type 2 diabetic patients.

坎地沙丁对2型糖尿病患者白蛋白尿影响的给药时间差异。

• 发表时间: 2009
• 期刊: Hypertension Research. 32
• 作者: Shimizu H;Okada S;et al
• 通讯作者: et al

Aberrant histone modifications at the thyrotropin-releasing hormone gene in resistance to thyroid hormone: analysis of F455S mutant thyroid hormone receptor.

• DOI: 10.1210/en.2008-1738
• 发表时间: 2009-07
• 期刊: Endocrinology
• 影响因子: 4.8
• 作者: Ryohei Umezawa;M. Yamada;Kazuhiko Horiguchi;S. Ishii;K. Hashimoto;S. Okada;T. Satoh;M. Mori