Study on the role of ceramide kinase in the macrophage-function

神经酰胺激酶在巨噬细胞功能中的作用研究

• 批准号: 23780344
• 负责人: MITSUTAKE Susumu
• 金额: $ 2.83万
• 依托单位: Saga University (2013)Hokkaido University (2011-2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 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-23780344/
• 关键词: ceramide; ceramide kinase; ceraide 1-phosphate; MCP-1; obesity; diabetes; ceramide 1-phosphate; セラミド; セラミドキナーゼ; セラミド1-リン酸

Chronic and low-grade inflammation is associated with the initial steps of obesity. Ceramide kinase (CERK) is an enzyme which phosphorylates ceramide to produce ceramide 1-phosphate. Recently, evidence has emerged that CERK has a role in inflammatory signaling of immune cells. Since obesity is accompanied with chronic, low-grade inflammation, we examined whether CERK might involved using CERK-null mice. We determined that CERK deficiency suppresses diet-induced increases in body weight, and improves glucose intolerance. Furthermore, we demonstrated that CERK deficiency attenuates MCP-1/CCR2 signaling in macrophages infiltrating adipose tissue, resulting in the suppression of inflammation in adipose, which might otherwise lead to obesity and diabetes.

慢性和低度炎症与肥胖的初始步骤有关。神经酰胺激酶（ceramidkinase，CERK）是一种磷酸化神经酰胺产生1-磷酸神经酰胺的酶。最近，有证据表明CERK在免疫细胞的炎症信号传导中起作用。由于肥胖伴随着慢性、低度炎症，我们使用CERK缺失小鼠研究了CERK是否可能涉及。我们确定CERK缺乏抑制饮食诱导的体重增加，并改善葡萄糖耐受不良。此外，我们证明了CERK缺乏减弱了巨噬细胞浸润脂肪组织中的MCP-1/CCR 2信号传导，导致脂肪中炎症的抑制，否则可能导致肥胖和糖尿病。

项目成果

Vitamins & Hormones 91 "Obesity"

维生素

• 发表时间: 2013
• 作者: S. Mitsutake;and Y. Igarashi
• 通讯作者: and Y. Igarashi

Dynamic Modification of Sphingomyelin in Lipid Microdomains Controls Development of Obesity, Fatty Liver, and Type 2 Diabetes

• DOI: 10.1074/jbc.m111.255646
• 发表时间: 2011-08-12
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Mitsutake, Susumu;Zama, Kota;Igarashi, Yasuyuki
• 通讯作者: Igarashi, Yasuyuki

A sensitive cell-based method to screen for selective inhibitors of SMS1 or SMS2 using HPLC and a fluorescent substrate.

• DOI: 10.1016/j.chemphyslip.2012.09.003
• 发表时间: 2012-10
• 期刊: Chemistry and physics of lipids
• 影响因子: 3.4
• 作者: Kota Zama;S. Mitsutake;Ken Watanabe;T. Okazaki;Y. Igarashi

Glycolipid & Sphingolipid Biology

糖脂

• 发表时间: 2012
• 作者: "SMS2 is implicated as a novel regulator of lipid microdomain structure and function"Mitsutake;K. Zama;T. Yoshida;H. Takemoto;T. Okazaki;Y. Igarashi
• 通讯作者: Y. Igarashi

Oral administration of phytosphingosine improves high-fat diet-induced glucose intolerance Bioscience

口服植物鞘氨醇可改善高脂饮食引起的葡萄糖不耐受

• 发表时间: 2013
• 期刊: Biotechnology, and Biochemistry
• 作者: Murakami;S. Mitsutake;N. Kobayashi;J. Matsuda;A. Suzuki;T. Shigyo;Y. Igarashi
• 通讯作者: Y. Igarashi