Study of molecular function of A170 as a factor for food intake regulation

A170 作为食物摄入调节因子的分子功能研究

• 批准号: 21790223
• 负责人: WARABI Eiji
• 金额: $ 2.75万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790223/
• 关键词: 摂食調節; メタボリックシンドローム; レプチン; A170; Sequestosomel; p62; レプチン抵抗性

Deficiency of A170, a scaffold protein for aPKC, causes mature-onset obesity in mice, but the mechanisms of the abnormal weight gain are unclear. I found that hyperphagia is the major cause of obesity in A170-deficient (KO) mice. KO and wild-type mice exhibited the same energy expenditure, and food restriction reversed obesity and glucose intolerance in the KO mice. Although their feeding responses to intracerebroventricular administration of an anorexigenic αMSH agonist and the orexigenic peptide NPY were normal, leptin did not induce anorexia, even in young, pre-obese KO mice. Immunohistochemical analyses revealed that A170 was normally expressed in leptin-responsive POMC- or NPY-expressing hypothalamic neurons. Importantly, although the leptin-induced phosphorylation of STAT3 on tyrosine was normal, the translocation of the phosphorylated STAT3 into the nucleus was defective in the KO hypothalamus. We propose that A170 is a novel regulator of leptin's anorectic signaling cascade in the central nervous system.

A170（aPKC 的支架蛋白）的缺乏会导致小鼠出现成熟性肥胖，但体重异常增加的机制尚不清楚，我发现食欲过盛是 A170 缺陷 (KO) 小鼠肥胖的主要原因。野生型小鼠表现出相同的能量消耗，并且食物限制逆转了 KO 小鼠的肥胖和葡萄糖不耐症，尽管它们对脑室内施用抑制食欲的 αMSH 激动剂有进食反应。且促食欲肽 NPY 正常，即使在年轻的肥胖前 KO 小鼠中，瘦素也不会诱发厌食症。 -诱导的STAT3酪氨酸磷酸化正常，磷酸化STAT3易位到细胞核中我们认为 A170 是中枢神经系统中瘦素厌食信号级联的新型调节剂。

项目成果

A novel mechanism of leptin resistance in sequestosome1- deficient mice.

Sequestosome1 缺陷小鼠瘦素抵抗的新机制。

• 发表时间: 2009
• 作者: Harumi Harada; Eiji Warabi; Taizo Matsuki; Kosuke Okada; Toru Yanagawa; Takeshi Sakurai; Tetsuro Ishii
• 通讯作者: Tetsuro Ishii

マクロファージの抗酸化ストレス応答-転写因子Nrf2と誘導タンパク質の役割

巨噬细胞的抗氧化应激反应-转录因子Nrf2和诱导蛋白的作用

• 发表时间: 2010
• 作者: 石井哲郎;柳川徹;蕨栄治
• 通讯作者: 蕨栄治

DEFICIENCY OF SEQUESTOSOME1/P62/A170 IN MICE IS ASSOCIATED WITH METABOLIC SYNDROME : (III) NON-DIPPER TYPE HYPERTENSION

小鼠中 Sequestosome1/P62/A170 的缺乏与代谢综合征相关：(III) 非杓型高血压

• 发表时间: 2010
• 作者: E.Warabi; S.Sakai; T.Yanagawa; H.Harada; R.C.M.Siow; G.E.Mann; T.Ishii
• 通讯作者: T.Ishii

UVB誘導性アポトーシスに対するSequestosome1/p62/A170の役割

Sequestosome1/p62/A170 对 UVB 诱导细胞凋亡的作用

• 发表时间: 2010
• 作者: 木村伸太郎;川内泰弘;蕨栄治;石井哲郎
• 通讯作者: 石井哲郎

Cochlear protection from acoustic injury by inhibitors of p38 mitogen-activated protein kinase and sequestosome 1 stress protein.

p38 丝裂原激活蛋白激酶和隔离体 1 应激蛋白抑制剂可保护耳蜗免受声损伤。

• 发表时间: 2010
• 作者: Tabuchi K; Oikawa K; Hoshino T; Nishimura B; Hayashi K; Yanagawa T; Warabi E; Ishii T; Tanaka S; Hara A.
• 通讯作者: Hara A.