Functional analysis of a novel metabolic syndrome related gene

一种新型代谢综合征相关基因的功能分析

• 批准号: 18591012
• 负责人: HOTTA Kikuko
• 金额: $ 2.57万
• 依托单位: The Institute of Physical and Chemical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591012/
• 关键词: MTMR9; Hypothalamus; Obesity; Metabolic syndrome; レプチン

SNPs in the obesity-related gene 3, that is myotubularin-related protein 9 (MTMR9) gene, was associated with obesity and hypertension. The mRNA with risk alleles of SNPs existed in 37UTR was less stable that that without risk alleles, suggesting that the mRNA levels of MTMR9 would be reduced in obese patients. Both the transcript and protein of MTMR9 were detected in the rodent lateral hypothalamic area as well as in the arcuate nucleus, an the protein co-existed with orexin, meanin concentrating hormone, neuropeptide Y (NPY) and proopiomelanocrotin. MTMR9 is belongs to myotularin family that possesses protein-tyrosine phosphatase activities. MTMR9, however, lacks phosphatase activity. MTMR9 interacts active phosphatase MTMR6 and MTMR7. MTMR9 and MTMR7 proteins were expressed in the same cell, suggesting that MTMR9 could act in the haypothalamic region together with MTMR7. The levels of MTMR9 transcript in the murine hypothalamic region increased after fasting and were decreased by a high-fat-diet in parallel with NPY and agouti-relate protein (AGRP). Thus, MTMR9 would be involved in appetite regulation. The level of MTMR9 transcript did not differ between ob/ob or db/db and control mice. These data suggested that MTMR9 may be the downstream of lepin signal. We identified the gentic variations in MTMR9 tha may influence the risk of obesity and hypertension in a large-scale case-control association study. We have demonstrated that the possibility that MTMR9 could involved in appetite regulation.

肥胖相关基因3（即肌管蛋白相关蛋白9（MTMR9）基因）中的SNP与肥胖和高血压有关。 37UTR中存在具有SNP风险等位基因的mRNA的mRNA不那么稳定，即没有风险等位基因，这表明肥胖患者的mTMR9 mRNA水平将降低。在啮齿动物下丘脑区域以及弧形核中都检测到MTMR9的转录本和蛋白质，该蛋白与Orexin，Meanin浓缩激素，神经肽Y（NPY）和肌蛋白酶素共存。 MTMR9属于具有蛋白质酪氨酸磷酸酶活性的肌蛋白家族。但是，MTMR9缺乏磷酸酶活性。 MTMR9与活性磷酸酶MTMR6和MTMR7相互作用。 MTMR9和MTMR7蛋白在同一细胞中表达，这表明MTMR9可以与MTMR7一起在Haypothalamic区域作用。禁食后鼠下丘脑区域中MTMR9转录物的水平升高，并通过与NPY和Agouti-Chareate蛋白（AGRP）并联的高脂含量降低。因此，MTMR9将参与食欲调节。 OB/OB或DB/DB和对照小鼠的MTMR9转录物水平没有差异。这些数据表明MTMR9可能是Lepin信号的下游。在大规模的病例对照协会的研究中，我们确定了MTMR9 THA的绅士变化可能影响肥胖和高血压的风险。我们已经证明了MTMR9可能参与食欲调节的可能性。

项目成果

Association of single-nucleotide polymorphisms in MTMR9 gene with obesity

• DOI: 10.1093/hmg/ddm260
• 发表时间: 2007-12-15
• 期刊: HUMAN MOLECULAR GENETICS
• 影响因子: 3.5
• 作者: Yanagiya, Takahiro;Tanabe, Atsushi;Hotta, Kikuko
• 通讯作者: Hotta, Kikuko

大規模SNP解析により同定した新たな肥満関連遺伝子

通过大规模SNP分析鉴定出新的肥胖相关基因

• 发表时间: 2007
• 作者: 堀田紀久子;柳谷隆宏;浜口和之;飯田有俊;斎藤督;関根章博;高橋篤;角田達彦;鎌谷直之;中村祐輔
• 通讯作者: 中村祐輔

「研究成果報告書概要(欧文)」より

摘自《研究结果报告摘要（欧洲）》

• 发表时间: 2006
• 期刊: Seibutsu Butsuri 46(1)
• 作者: Yasushi Shigeri;Keiko Shimamoto
• 通讯作者: Keiko Shimamoto

肥満の検査方法及び肥満の予防又は治療薬のスクリーニング方法

肥胖症检测方法及肥胖症预防或治疗药物筛选方法

• 发表时间: 2007

Association of single-nucleotide polymorphims in MTMR9 genewith obesity

MTMR9基因单核苷酸多态性与肥胖的关联

• 发表时间: 2007
• 期刊: Hum. Mol.Genet. 16(24)
• 作者: Yanasiya;T.;Tanabe;A.;Iida;A.;Saito;S.;Sekine;A.;Takahashi;A.;Tsunoda;T.;Kamohara;S.;Nakata;Y.;Kotani;K.;Komatsu;R.;Itoh;N.;Mineo;I.;Wada;J.;Masuzaki;H.;Yoneda;M.;Nakajima;A.;Miyazaki;S.;Tokunaga;K.;Kawamoto;M.;Funa
• 通讯作者: Funa