The role of protein tyrosine phosphatase-1B in the hypothalamic inflammation induced by a high fat diet

• Project/Area Number: 15K09381
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Nagoya University
• Principal Investigator: Banno Ryoichi 名古屋大学, 医学系研究科, 講師 (80597865)
• Co-Investigator(Kenkyū-buntansha): 有馬 寛 名古屋大学, 医学系研究科, 教授 (50422770)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 肥満 / 炎症 / グリア細胞 / アストロサイト / ミクログリア / PTP1B / 高脂肪食 / 視床下部 / 視床下部炎症 / STAT3リン酸化

Outline of Final Research Achievements

Hypothalamus plays an important role in the regulation of energy balance. A high fat diet induces hypothalamic inflammation, which is known to play a causal role in obesity. We investigated the role of protein tyrosine phosphatase-1B（PTP1B), a regulator of leptin, insulin and inflammatory signaling, in the hypothalamic inflammation induced by a high fat diet. Our results suggest that PTP1B in the microglia enhances hypothalamic inflammation, and PTP1B in the astrocye increases body weight under a high fat diet conditions.

Research Products

• [Journal Article] Deficiency of PTP1B Attenuates Hypothalamic Inflammation via Activation of the JAK2-STAT3 Pathway in Microglia. (2017)
  • Author(s): Tsunekawa T, Banno R, Mizoguchi A, Sugiyama M, Tominaga T, Onoue T, Hagiwara D, Ito Y, Iwama S, Goto M, Suga H, Sugimura Y, Arima H.
  • Journal Title: EBioMedicine Volume: 16 Pages: 172-183
  • DOI: 10.1016/j.ebiom.2017.01.007
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Magnetic-activated cell sorting法を用いた視床下部アストロサイトの単離と機能解析 (2017)
  • Author(s): 杉山 摩利子、坂野 僚一、滝 啓吾、溝口 暁、恒川 卓、高木 博史、伊藤 禎浩、小峯 起、山中宏二、有馬 寛
  • Organizer: 第38回日本肥満学会
• [Presentation] Analysis of roles of glial cell subtypes in hypothalamic inflammation induced by a high fat diet (2017)
  • Author(s): Sugiyama M, Banno R, Taki K, Mizoguchi A, Tsunekawa T, Takagi H, Ito Y, Komine O, Yamanaka K, Arima H
  • Organizer: Obesity Society's 2017 Annual Meeting
  • Int'l Joint Research
• [Presentation] Deficiency of PTP1B attenuates hypothalamic inflammation induced by high fat diet via the activation of JAK2-STAT3 signaling pathway in the microglial cells (2016)
  • Author(s): Tsunekawa T, Banno R, Mizoguchi A, Sugiyama M, Tominaga T, Onoue T, Ito Y, Goto M, Arima H
  • Organizer: Obesity Society's 2016 Annual Meeting
  • Place of Presentation: Ｎew Orleans USA
  • Year and Date: 2016-11-01
  • Int'l Joint Research
• [Presentation] ミクログリアのPTP1Bは視床下部炎症を増強する (2016)
  • Author(s): 恒川卓、坂野僚一、杉山摩利子、富永隆史、尾上剛史、後藤資実、有馬寛
  • Organizer: 第59回 日本糖尿病学会年次学術総会
  • Place of Presentation: 国立京都国際会館 ロームシアター京都（京都府 京都市）
  • Year and Date: 2016-05-19
• [Presentation] PTP1B deficiency activates JAK2-STAT3 signaling pathway downstream of TNFα receptor in the microglial cells resulting in the attenuation of hypothalamic inflammation under HFD conditions (2015)
  • Author(s): 坂野僚一
  • Organizer: CREST international symposium 2015
  • Place of Presentation: 生理学研究所（愛知県 岡崎市）
  • Year and Date: 2015-12-26
  • Int'l Joint Research / Invited
• [Presentation] Deficiency of PTP1B attenuates hypothalamic inflammation via the activation of JAK2-STAT3 signaling pathway in the microglial cells under high fat diet conditions. (2015)
  • Author(s): 坂野 僚一、杉山 摩利子、富永 隆史、尾上 剛史、恒川 卓、後藤 資実、有馬 寛
  • Organizer: 2015 Keystone Symposia Conference
  • Place of Presentation: ウェスティン都ホテル京都（京都府 京都市）
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] PTP1B deficiency attenuates hypothalamic inflammation through the activation of Jak2-Stat3 signaling pathway downstream of TNFα receptor under high fat diet conditions. (2015)
  • Author(s): 恒川 卓、坂野 僚一、杉山 摩利子、富永 隆史、尾上 剛史、後藤 資実、有馬 寛
  • Organizer: Neuroscience 2015
  • Place of Presentation: シカゴ, アメリカ
  • Year and Date: 2015-10-17
  • Int'l Joint Research
• [Presentation] Mechanisms by which PTP1B affects energy balance (2015)
  • Author(s): 坂野僚一
  • Organizer: The 46th NIPS International Symposium
  • Place of Presentation: 名古屋国際会議場（愛知県 名古屋市）
  • Year and Date: 2015-10-02
  • Int'l Joint Research / Invited
• [Presentation] 視床下部PTP1BはJAK2-STAT3の脱リン酸化を介して視床下部炎症を増強する (2015)
  • Author(s): 恒川 卓、坂野 僚一、富永 隆史、尾上 剛史、柴田 みゆき、後藤 資実、大磯 ユタカ、有馬 寛
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 海峡メッセ下関（山口県 下関市）
  • Year and Date: 2015-05-21