Functional analysis of a novel metabolic syndrome related gene

• Project/Area Number: 18591012
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: HOTTA Kikuko The Institute of Physical and Chemical Research, Laboratory for Obesity, Laboratory Head (30360639)
• Co-Investigator(Kenkyū-buntansha): YANAGIYA Takahiro RIKEN, Laboratory for Obesity, Research Scientist (40322698) ; TANABE Atsushi RIKEN, Laboratory for Obesity, Research Scientist (30373327)
• Project Period (FY): 2006 – 2007
• Project Status: Completed (Fiscal Year 2007)
• Budget Amount: ¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: MTMR9 / Hypothalamus / Obesity / Metabolic syndrome / レプチン

Research Abstract

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.

Research Products

• [Journal Article] Association of single-nucleotide polymorphisms in MTMR9 gene with obesity (2007)
  • Author(s): Yanagiya, 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., Funahashi, T.,Hamaguchi, K.,Tanaka, K.,Yamada, K., Hanafusa, T., Oikawa, S., Yoshimatsu, H., Nakao, K., Sakata, T., Matsuzawa, Y., Kamatani, N., Nakamuara, Y., Hotta, K
  • Journal Title: Hum. Mol. Genet. 16 Pages: 3017-3026
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Association of single-nucleotide polymorphims in MTMR9 genewith obesity (2007)
  • Author(s): 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., Funahashi, T., Hamaguchi, K., Tanaka, K., Yamada, K., Hanafusa, T., Oikawa, S., Yoshimatsu, H., Nakao, K., Sakata, T., Matsuzawa, Y., Kamatani, N., Nakamura, Y.
  • Journal Title: Hum. Mol.Genet. 16(24) Pages: 3017-3026
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Association of single-nucleotide polymorphisms in MTMR9 gene with obesity (2007)
  • Author(s): Yanagiya, 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., Funahashi, T., Hamaguchi, K., Tanaka, K., Yamada, K., Hanafusa, T., Oikawa, S., Yoshimatsu, H., Nakao, K., Sakata, T., Matsuzawa, Y., Kamatani, N., Nakamura, Y., Hotta, K
  • Journal Title: Hum.Mol.Genet. 16 Pages: 3017-3026
  • Peer Reviewed
• [Presentation] 大規模SNP解析により同定した新たな肥満関連遺伝子 (2007)
  • Author(s): 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
  • Organizer: 日本人類遺伝学会第52回大会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2007-09-14
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] 「研究成果報告書概要(欧文)」より
  • Author(s): Kikuko Hotta, Takahiro Yanagiya, Kazuyuki Hamaguchi, Aritoshi Iida, Susumu Saito, Akihiro Sekine, Atsushi Takahashi, Tatsuhiko Tsunoda, Naoyuki Kamatani, Yusuke Nakamura
  • Organizer: The 52nd Annual Meeting of the Japan Society of Human Genetics
• [Patent(Industrial Property Rights)] 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 (2007)
  • Inventor(s): 堀田紀久子, 柳谷隆宏
  • Industrial Property Rights Holder: 独立行政法人理化学研究所
  • Industrial Property Number: 2007-163399
  • Filing Date: 2007-06-21
  • Description: 「研究成果報告書概要(和文)」より