The role of unfolded protein response in brown adipocytes

• Project/Area Number: 15K19516
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: Hiroshima University
• Principal Investigator: Asada Rie 広島大学, 医歯薬保健学研究院(医), 助教 (70751882)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 小胞体ストレス応答 / 褐色脂肪細胞 / UCP1 / IRE1α / XBP1

Outline of Final Research Achievements

The unfolded protein response (UPR) not only resolves endoplasmic reticulum (ER) stress, but also regulates cellular physiological functions such as proliferation, differentiation, and energy metabolism. In this study, we explored the physiological role of UPR in brown adipocytes. We found the one of UPR branch, IRE1alpha -XBP1 pathway, is crucial for the transcriptional induction of thermogenin UCP1. We also revealed that tissue-specific ER stress transducer BBF2H7 is involved in the differentiation of brown adipocytes.

Research Products

• [Journal Article] Multivesicular body formation enhancement and exosome release during endoplasmic reticulum stress (2016)
  • Author(s): Kanemoto S, Nitani R, Murakami T, Kaneko M, Asada R, Matsuhisa K, Saito A, Imaizumi K
  • Journal Title: Biochemical and biophysical research communications Volume: 480 Issue: 2 Pages: 166-172
  • DOI: 10.1016/j.bbrc.2016.10.019
  • Peer Reviewed
• [Journal Article] The androgen-induced protein AIbZIP facilitates proliferation of prostate cancer cells through downregulation of p21 expression (2016)
  • Author(s): Cui X, Cui M, Asada R, Kanemoto S, Saito A, Matsuhisa K, Kaneko M, Imaizumi K
  • Journal Title: Scientific reports Volume: 6 Issue: 1 Pages: 37310-37310
  • DOI: 10.1038/srep37310
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization. (2015)
  • Author(s): Kanemoto S, Kobayashi Y, Yamashita T, Miyamoto T, Cui M, Asada R, Cui X, Hino K, Kaneko M, Takai T, Matsuhisa K, Takahashi N, Imaizumi K.
  • Journal Title: J Cell Sci Volume: 128 Pages: 4353-4365
  • DOI: 10.1242/jcs.176057
  • Peer Reviewed / Open Access
• [Journal Article] IRE1a-XBP1 is a novel branch in the transcriptional regulation of Ucp1 in brown adipocytes. (2015)
  • Author(s): Asada R, Kanemoto S, Matsuhisa K, Hino K, Cui M, Cui X, Kaneko M, Imaizumi K.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 16580-16580
  • DOI: 10.1038/srep16580
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] OASIS modulates hypoxia pathway activity to regulate bone angiogenesis. (2015)
  • Author(s): Min Cui, Soshi Kanemoto, Xiang Cui, Masayuki Kaneko, Rie Asada, Koji Matsuhisa, Keiji Tanimoto, Yuki Yoshimoto, Chisa Shukunami, Kazunori Imaizumi.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 16455-16455
  • DOI: 10.1038/srep16455
  • Peer Reviewed / Open Access
• [Journal Article] Promotion of cancer cell proliferation by cleaved and secreted luminal domains of ER stress transducer BBF2H7. (2015)
  • Author(s): Iwamoto H, Matsuhisa K, Saito A, Kanemoto S, Asada R, Hino K, Takai T, Cui M, Cui X, Kaneko M, Arihiro K, Sugiyama K, Kurisu K, Matsubara A, Imaizumi K.
  • Journal Title: Plos One Volume: 10 Issue: 5 Pages: 1-17
  • DOI: 10.1371/journal.pone.0125982
  • Peer Reviewed / Open Access
• [Presentation] ER-resident transmembrane transcription factor OASIS plays important role in DNA damage response (2016)
  • Author(s): Asada R, Kikushima K, Cui M, Imaizumi K
  • Organizer: ASCB Annual Meeting
  • Place of Presentation: サンフランシスコ, 米国
  • Year and Date: 2016-12-05
  • Int'l Joint Research
• [Presentation] アストロサイトの細胞分化における小胞体膜貫通型転写因子OASISの働き (2016)
  • Author(s): 浅田梨絵、崔旻、今泉和則
  • Organizer: 第59回日本神経化学会大会
  • Place of Presentation: 福岡市
  • Year and Date: 2016-09-08
• [Presentation] IRE1α-XBP1経路による褐色脂肪細胞の熱産生遺伝子Ucp1の発現制御 (2015)
  • Author(s): 浅田梨絵、今泉和則
  • Organizer: 第38回日本分子生物学会年会、第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-03
• [Presentation] 褐色脂肪細胞における小胞体ストレス応答の役割 (2015)
  • Author(s): 浅田梨絵、今泉和則
  • Organizer: 第10回小胞体ストレス研究会
  • Place of Presentation: 淡路夢舞台国際会議場（兵庫県淡路市）
  • Year and Date: 2015-11-30
• [Presentation] 小胞体ストレス応答による褐色脂肪細胞の機能調節 (2015)
  • Author(s): 浅田梨絵、今泉和則
  • Organizer: 第56回日本生化学会・中国・四国支部例会
  • Place of Presentation: 島根大学（島根県松江市）
  • Year and Date: 2015-05-30
• [Remarks] エネルギー代謝を司る褐色脂肪細胞の働きを調節する新規経路の発見～肥満治療へ新しい可能性～