Mechanism involved in resistance to diet-induced obesity observed in protein phosphatase PPM1L knockout mice.

• Project/Area Number: 15K08293
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Tohoku University
• Principal Investigator: Kobayashi Takayasu 東北大学, 遺伝子実験センター, 准教授 (10221970)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: プロテインホスファターゼ

Outline of Final Research Achievements

Obesity is major risk factor for diabetes and cardiovascular diseases. In an earlier study using quantitative trait loci (QTL) analysis in mice, protein phosphatase Ppm1l was identified as a gene connected to obesity and other metabolic syndrome traits (Chen et al, 2008), but the underlying mechanism remains unclear. PPM1L-KO mice were protected against high fat diet-induced obesity. This was partly due to diminished food intake. PPM1L-KO mice exhibit morphological abnormalities in the central nerve system including reduction of striatum, corpus callosum and anterior commissure, suggesting that defect of neural network in CNS may result in reduced appetite. Using recently described proximity-dependent biotin labeling (BioID) technique, a number of nuclear envelope associated proteins were identified as interacting partner of PPM1L.

Research Products

• [Journal Article] A novel indole compound MA-35 attenuates renal fibrosis by inhibiting both TNF-α and TGF-β₁ pathways (2017)
  • Author(s): Shima, H., Sasaki, K., Suzuki, T., Mukawa, C., Obara, T., Oba, Y., Matsuo, A., Kobayashi, T., Mishima, E., Watanabe, S., Akiyama, Y., Kikuchi, K., Matsuhashi, T., Oikawa, Y., Nanto, F., Ho, H.J., Suzuki, C., Saigusa, D., Masamune, A., Tomioka, Y., Masaki, T., Ito, S., Hayashi, K.I., Abe, T.
  • Journal Title: Sci Rep. Volume: 7 Issue: 1 Pages: 1884-1884
  • DOI: 10.1038/s41598-017-01702-7
  • Peer Reviewed / Open Access
• [Journal Article] Targeted disruption of the mouse protein phosphatase ppm1l gene leads to structural abnormalities in the brain. (2016)
  • Author(s): Kusano, R., Kousuke Fujita, K., Yasuharu Shinoda, Y., Nagaura, Y., Kiyonari, H., Abe, T, Watanabe, T., Matsui, Y., Fukaya, M., Sakagami, H., Sato, T., Funahashi, J.-I., Ohnishi, M., Tamura, S., Kobayashi, T.
  • Journal Title: FEBS Letters Volume: 590 Issue: 20 Pages: 3603-3615
  • DOI: 10.1002/1873-3468.12429
  • Peer Reviewed
• [Journal Article] Regulation of cellular functions by protein phosphatase PPM family members (2015)
  • Author(s): 小林孝安
  • Journal Title: 生化学 Volume: 87 Issue: 5 Pages: 525-530
  • DOI: 10.14952/SEIKAGAKU.2015.870525
  • ISSN: 0037-1017
  • Year and Date: 2015-10-25
• [Journal Article] Mammalian Bcnt/Cfdp1, a potential epigenetic factor characterized by an acidic stretch in the disordered N-terminal and Ser250 phosphorylation in the conserved C-terminal regions (2015)
  • Author(s): Iwashita, S., Suzuki, T., Yasuda, T., Nakashima, K., Sakamoto, T., Kohno, T., Takahashi, I., Kobayashi, T., Ohno-Iwashita, Y., Imajoh-Ohmi, S., Song, S. Y., Dohmae, N.
  • Journal Title: Biosci Rep Volume: 35 Issue: 4 Pages: 1-12
  • DOI: 10.1042/bsr20150111
  • Peer Reviewed / Open Access
• [Presentation] プロテインホスファターゼPPM1Lの肥満形成への関与のメカニズムの解明 (2016)
  • Author(s): 小林孝安
  • Organizer: 第89回 日本生化学会大会
  • Place of Presentation: 仙台国際センター(宮城県仙台市)
  • Year and Date: 2016-09-25
• [Presentation] プロテインホスファターゼPPM1Lの肥満形成への関与のメカニズムの解明 (2016)
  • Author(s): 小林孝安
  • Organizer: 第7回日本プロテインホスファターゼ研究会学術集会
  • Place of Presentation: 自然科学研究機構大会議室（愛知県岡崎市）
  • Year and Date: 2016-01-29
• [Presentation] Two post-translational modifications in mammalian B cnt/Cfdp1, a potential epigen etic factor: S250 phosphorylation and K268 acetylation in the conserved C-termin al region (2015)
  • Author(s): 岩下 新太郎, 中島 健太郎, 鈴木 健裕, 安田 武嗣, 坂本 泰一, 河野 俊之, 高橋 一朗, 小林 孝安, 大野 岩下 淑子, 今城 大海 忍, 堂前 直, 宋 時栄
  • Organizer: 第88回日本生化学会大会/第38回日本分子生物学会年会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] ノックアウトマウスを用いたプロテインホスファターゼPPM1Lの新規機能解明 (2015)
  • Author(s): 藤田 宏介, 篠田 康晴, 永浦 裕子, 草野 理恵, 渡邊 利雄, 松居 靖久, 阪上 洋行,佐藤達也, 舟橋淳一, 大西 素子, 田村 眞理, 小林 孝安,
  • Organizer: 日本生化学会東北支部会第81回例会
  • Place of Presentation: 東北大学片平さくらホール（宮城県仙台市）
  • Year and Date: 2015-05-09