The role of ILDR2 in ER stress and hepatic steatosis

• Project/Area Number: 15K19523
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Jichi Medical University
• Principal Investigator: Watanabe Kazuhisa 自治医科大学, 医学部, 助教 (60724416)
• Research Collaborator: Leibel Rudolph Columbia University, Department of Pediatrics, Professor
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 脂肪肝 / ERストレス / 小胞体ストレス

Outline of Final Research Achievements

A diabetes susceptibility gene, immunoglobulin-like domain containing receptor 2 (Ildr2), encodes a transmembrane protein localized to the endoplasmic reticulum membrane that is closely related to hepatic lipid metabolism. The livers of ob/ob mice in which Ildr2 is transiently overexpressed are relieved of hepatic steatosis. However, the molecular mechanisms through which ILDR2 affects these changes in hepatic lipid metabolism remain unknown.
We purified ILDR2-containing protein complexes using tandem affinity purification tagging and identified several ILDR2 binding proteins. This result supports a novel link between ILDR2 and ILDR2-interacting proteins and suggest that ILDR2 is involved in a novel pathway in hepatic steatosis.

Research Products

• [Int'l Joint Research] Columbia University(米国)
• [Int'l Joint Research] Naomi Berrie Diabetes Center/Columbia University Medical Center(米国)
• [Journal Article] ZNF70, a novel ILDR2-interacting protein, contributes to the regulation of HES1 gene expression (2016)
  • Author(s): Kazuhisa Watanabe, Kazuhiro Nakayama, Satoshi Ohta, Kenji Tago, Supichaya Boonvisut, Elizabeth J. Millings, Stuart G. Fischer, Charles A. LeDuc, Rudolph L. Leibel, Sadahiko Iwamoto
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 477 Pages: 712-716
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Lipogenesis and ER stress are mediated in part by USF1 effects on transcriptional regulation of ILDR2 (2015)
  • Author(s): Watanabe K, Millings E, Fischer S, LeDuc C, Leibel R
  • Journal Title: Diabetes Volume: 64
  • Peer Reviewed / Int'l Joint Research
• [Presentation] 新規糖尿病感受性遺伝子Ildr2の機能解析 (2016)
  • Author(s): 渡邉和寿、Millings Elizabeth、Fischer Stuart、Leduc Charles、中山 一大、Leibel Rudolph、岩本 禎彦
  • Organizer: 第37回 日本肥満学会
  • Place of Presentation: 東京ファッションタウン（東京都・江東区）
  • Year and Date: 2016-10-07
• [Presentation] 新規糖尿病感受性遺伝子Ildr2の機能解析 (2016)
  • Author(s): 渡邉和寿、Millings Elizabeth、Fischer Stuart、Leduc Charles、中山 一大、Leibel Rudolph、岩本 禎彦
  • Organizer: 第59回 日本糖尿病学会
  • Place of Presentation: 国立京都国際会館（京都府・京都市）
  • Year and Date: 2016-05-20
• [Presentation] 新規糖尿病感受性遺伝子Ildr2の機能解析 (2016)
  • Author(s): 渡邉和寿、Millings Elizabeth、Fischer Stuart、Leduc Charles、中山 一大、Leibel Rudolph、岩本 禎彦
  • Organizer: 第70回 日本栄養・食糧学会
  • Place of Presentation: 武庫川女子大学（兵庫県・西宮市）
  • Year and Date: 2016-05-15
• [Presentation] Lipogenesis and ER stress are mediated in part by USF1 effects on transcriptional regulation of ILDR2. (2015)
  • Author(s): Watanabe K, Millings E, Fischer S, LeDuc C, Leibel R
  • Organizer: American Diabetes Association's 75th Scientific Sessions
  • Place of Presentation: Boston, USA
  • Year and Date: 2015-06-05
  • Int'l Joint Research
• [Presentation] 新規糖尿病感受性遺伝子Ildr2の機能解析 (2015)
  • Author(s): 渡邉和寿、Supichaya Boonvisut、中山 一大、Leibel Rudolph、岩本 禎彦
  • Organizer: 第58回 日本糖尿病学会
  • Place of Presentation: 海峡メッセ下関 （山口）
  • Year and Date: 2015-05-21
• [Remarks]
  • URL: http://www.jichi.ac.jp/laboratory/molecula/human/