Role of integrated stress response in adipocyte

• Project/Area Number: 17K09862
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokushima
• Principal Investigator: MIYAKE Masato 徳島大学, 先端酵素学研究所(プロテオ), 講師 (30588976)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 肥満 / 糖尿病 / 臓器連関 / 摂食調節 / ストレス応答 / 摂食 / 脂肪細胞 / 内分泌 / 脂肪 / 統合的ストレス応答 / 小胞体ストレス / 代謝

Outline of Final Research Achievements

In this study, we investigated the role of integrated stress response (ISR), which is one of stress response signaling and activated in metabolic disorders, in adipocytes of mice. The ISR did not affect metabolic function in adipocyte. However, activation of the ISR induced GDF15 expression that is known to repress appetite in adipocyte. The ISR-induced GDF15 repressed high-fat diet specific food intake and improved diet-induced obesity.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果によって統合的ストレス応答の活性化は、細胞自律的なストレスへの対応の役割だけでなく、内分泌ホルモンなどを介した臓器連関によって個体レベルでストレスに応答して恒常性を保つために機能していることが示唆された。また、脂肪細胞への適切な統合的ストレス応答の活性化は、摂食行動を制御する可能性が示され新たな肥満や糖尿病の治療標的となることがわかった。

Research Products

• [Journal Article] ER-resident sensor PERK is essential for mitochondrial thermogenesis in brown adipose tissue. (2020)
  • Author(s): Kato H, Okabe K, Miyake M, Hattori K, Fukaya T, Tanimoto K, Beini S, Mizuguchi M, Torii S, Arakawa S, Ono M, Saito Y, Sugiyama T, Funatsu T, Sato K, Shimizu S, Oyadomari S, Ichijo H, Kadowaki H, Nishitoh H.
  • Journal Title: Life science alliance Volume: 3 Issue: 3 Pages: 201900576-201900576
  • DOI: 10.26508/lsa.201900576
  • NAID: 120006980545
  • Peer Reviewed / Open Access
• [Journal Article] Nanosecond pulsed electric fields induce the integrated stress response via reactive oxygen species-mediated heme-regulated inhibitor (HRI) activation (2020)
  • Author(s): Hamada Yoshimasa、Furumoto Yuji、Izutani Akira、Taniuchi Shusuke、Miyake Masato、Oyadomari Miho、Teranishi Kenji、Shimomura Naoyuki、Oyadomari Seiichi
  • Journal Title: PLOS ONE Volume: 15 Issue: 3 Pages: e0229948-e0229948
  • DOI: 10.1371/journal.pone.0229948
  • NAID: 120006869528
  • Peer Reviewed / Open Access
• [Journal Article] Inter-Organ Metabolic Communication via the Unfolded Stress Response (2018)
  • Author(s): Miyake Masato, Oyadomari Seiichi.
  • Journal Title: Clinical calcium Volume: 28 Pages: 1548-1553
• [Journal Article] PERK-mediated translational control is required for collagen secretion in chondrocytes (2018)
  • Author(s): Hisanaga Satoshi、Miyake Masato、Taniuchi Shusuke、Oyadomari Miho、Morimoto Masatoshi、Sato Ryosuke、Hirose Jun、Mizuta Hiroshi、Oyadomari Seiichi
  • Journal Title: Scientific Reports Volume: 8 Issue: 1 Pages: 773-773
  • DOI: 10.1038/s41598-017-19052-9
  • NAID: 120006535034
  • Peer Reviewed / Open Access
• [Journal Article] A miR-327-FGF10-FGFR2-mediated autocrine signaling mechanism controls white fat browning (2017)
  • Author(s): Fischer Carina、Seki Takahiro、Lim Sharon、Nakamura Masaki、Andersson Patrik、Yang Yunlong、Honek Jennifer、Wang Yangang、Gao Yanyan、Chen Fang、Samani Nilesh J.、Zhang Jun、Miyake Masato、Oyadomari Seiichi、Yasue Akihiro、Li Xuri、Zhang Yun、Liu Yizhi、Cao Yihai
  • Journal Title: Nature Communications Volume: 8 Issue: 1 Pages: 2079-2079
  • DOI: 10.1038/s41467-017-02158-z
  • NAID: 120006535077
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ligand-induced rapid skeletal muscle atrophy in HSA-Fv2E-PERK transgenic mice. (2017)
  • Author(s): Miyake M, Kuroda M, Kiyonari H, Takehana K, Hisanaga S, Morimoto M, Zhang J, Oyadomari M, Sakaue H, Oyadomari S.
  • Journal Title: PLoS One. Volume: 12 Issue: 6 Pages: e0179955-e0179955
  • DOI: 10.1371/journal.pone.0179955
  • NAID: 120006812009
  • Peer Reviewed / Open Access
• [Journal Article] The Role of Heparin Cofactor Ⅱ in the Regulation of Insulin Sensitivity and Maintenance of Glucose Homeostasis in Humans and Mice (2017)
  • Author(s): Kurahashi K, Inoue S, Yoshida S, Ikeda Y, Morimoto K, Uemoto R, Ishikawa K, Kondo T, Yuasa T, Endo I, Miyake M, Oyadomari S, Matsumoto T, Abe M, Sakaue H, Aihara KI.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 24 Issue: 12 Pages: 1215-1230
  • DOI: 10.5551/jat.37739
  • NAID: 130006235273
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed / Open Access
• [Presentation] Preemptive Activation of the Integrated Stress Response in adipose tissue suppress food intake and improved obesity through growth and differentiation factor 15 (2019)
  • Author(s): Miyake Masato, Zhang Jun, Oyadomari Seiichi
  • Organizer: EMBO workshop Proteostasis: From organelles to organisms
  • Int'l Joint Research
• [Presentation] 脂肪細胞における統合的ストレス応答はGDF15を介した摂食抑制により食事性肥満を改善する (2018)
  • Author(s): 三宅 雅人、張 君、久永 哲、親泊 美帆、親泊 政一
  • Organizer: 第61回日本糖尿病学会年次学術集会
• [Presentation] 脂肪組織での統合的ストレス応答はDdit3-Gdf15経路による摂食抑制を介して肥満を改善する (2018)
  • Author(s): 三宅 雅人、張 君、親泊 政一
  • Organizer: 第39回日本肥満学会
• [Presentation] CRISPRスクリーンで同定した新規PERK経路制御因子の機能解明 (2018)
  • Author(s): 三宅 雅人、谷内 秀輔、親泊 政一
  • Organizer: 第13回小胞体ストレス研究会
• [Presentation] 脂肪細胞におけるストレス応答性転写因子ATF4の機能解明 (2018)
  • Author(s): 三宅 雅人、親泊 政一
  • Organizer: 第30回分子糖尿病学シンポジウム
• [Presentation] 小胞体ストレス応答因子PERKによる代謝調節機構 (2017)
  • Author(s): 三宅 雅人 , 親泊 政一
  • Organizer: 2017年度生命科学系学会合同年次大会
  • Invited
• [Remarks]
  • URL: http://www.genome.tokushima-u.ac.jp/dmb/DMB/homu.html