Molecular mechanism of cell-cell interaction in aging-induced adipose tissue inflammation

• Project/Area Number: 18K08508
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: Nagoya University
• Principal Investigator: Tanaka Miyako 名古屋大学, 環境医学研究所, 講師 (60622793)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: マクロファージ / 炎症 / 加齢 / inflammaging / 慢性炎症 / 脂肪細胞 / 線維化

Outline of Final Research Achievements

In this study, we focused on the adipose tissue remodeling to investigate the molecular mechanism of aging-induced adipose tissue inflammation. We found several genes that changes in the subcutaneous adipose tissue-specific manner with aging. We will generate the mice that these genes genetically knocked out or overexpressed to investigate the effects of them on aging. We also examined the adipose tissue inflammation and ectopic fat accumulation in artificially "rebounded" mice. Generally, it is said that rebound worsens metabolism compared to before weight loss, but in the results of this study, in rebound mice, the metabolism wasn't worsened but rather improved. In the future, I would like to study in more detail and give the accurate information.

Academic Significance and Societal Importance of the Research Achievements

高齢化社会を迎え，高齢者の健康や健康寿命に対し関心が集まっている。一方，加齢に伴い，皮下脂肪組織は減少し，逆に内臓脂肪組織が増加することが知られており，「皮膚粗鬆症」という概念も生まれている。本研究において見出した新たな遺伝子の役割を詳細に検討することで，加齢に伴う疾患の予防や治療に貢献できると考えている。また，これまで，リバウンドは減量する前よりも代謝が悪くなると考えられていたが，必ずしもそうではない可能性を見出した。今後，より詳細に検討し，リバウンドを起こす可能性があっても減量した方が健康に良い，というような研究成果に基づいた正しい情報を提供することで，ヒトの健康に寄与したい。

Research Products

• [Journal Article] Iron-rich Kupffer cells exhibit phenotypic changes during the development of liver fibrosis in NASH. (2021)
  • Author(s): Kanamori Y, Tanaka M, Itoh M, Ochi K, Ito A, Hidaka I, Sakaida I, Ogawa Y, Suganami T
  • Journal Title: iScience Volume: 24 Issue: 2 Pages: 2102032-2102032
  • DOI: 10.1016/j.isci.2020.102032
  • Peer Reviewed / Open Access
• [Journal Article] Digenic mutations in ALDH2 and ADH5 impair formaldehyde clearance and cause a multisystem disorder, AMeD syndrome (2020)
  • Author(s): Oka Y, Hamada M, Nakazawa Y, ..., Tanaka M, Suganami T, Nakada S, Mitsutake N, Hara Y, Kato K, ..., Kaneko H, Matsumoto N, Matsuda F, Matsuo K, Takahashi Y, Mashimo T, Kojima S, Ogi T
  • Journal Title: Science Advances Volume: 6 Issue: 51 Pages: 7197-7197
  • DOI: 10.1126/sciadv.abd7197
  • Peer Reviewed / Open Access
• [Journal Article] C-type lectin Mincle mediates cell death-triggered inflammation in acute kidney injury. (2020)
  • Author(s): Tanaka M, Saka-Tanaka M, Ochi K, Fujieda K, Sugiura Y, Miyamoto T, Kohda H, Ito A, Miyazawa T, Matsumoto A, Aoe S, Miyamoto Y, Tsuboi N, Maruyama S, Suematsu M, Yamasaki S, Ogawa Y, Suganami T.
  • Journal Title: J Exp Med. Volume: 217 Issue: 11
  • DOI: 10.1084/jem.20192230
  • Peer Reviewed / Open Access
• [Journal Article] Hollow fiber-combined glucose-responsive gel technology as an in vivo electronics-free insulin delivery system. (2020)
  • Author(s): Matsumoto A, Kuwata H, Kimura S, Matsumoto H, Ochi K, Moro-oka Y, Watanabe A, Yamada H, Ishii H, Miyazawa T, Chen S, Baba T, Yoshida H, Nakamura T, Inoue H, Ogawa Y, Tanaka M, Miyahara Y, Suganami T.
  • Journal Title: Commun. Biol. Volume: 3 Issue: 1 Pages: 313-313
  • DOI: 10.1038/s42003-020-1026-x
  • Peer Reviewed / Open Access
• [Journal Article] Ubiquitination of DNA Damage-Stalled RNAPII Promotes Transcription-Coupled Repair (2020)
  • Author(s): Nakazawa Y, Hara Y, Oka Y, Komine O, van den Heuvel D, Guo C, Daigaku Y, Isono M, He Y, Shimada M, Kato K, Jia N, Hashimoto S, Kotani Y, Miyoshi Y, Tanaka M, Sobue A, Mitsutake N, Suganami T, Masuda A, Ohno K, Nakada S, Mashimo T, Yamanaka K, Luijsterburg MS, Ogi T
  • Journal Title: Cell Volume: 19 Issue: 6 Pages: 1228-1244
  • DOI: 10.1016/j.cell.2020.02.010
  • NAID: 120006871293
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dipeptidyl peptidase-4 inhibition prevents nonalcoholic steatohepatitis?associated liver fibrosis and tumor development in mice independently of its anti-diabetic effects (2020)
  • Author(s): Kawakubo M, Tanaka M, Ochi K, Watanabe A, Saka-Tanaka M, Kanamori Y, Yoshioka N, Yamashita S, Goto M, Itoh M, Shirakawa I, Kanai S, Suzuki H, Sawada M, Ito A, Ishigami M, Fujishiro M, Arima H, Ogawa Y, Suganami T
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 983-983
  • DOI: 10.1038/s41598-020-57935-6
  • Peer Reviewed / Open Access
• [Journal Article] Molecular mechanism of obesity-induced adipose tissue inflammation; the role of Mincle in adipose tissue fibrosis and ectopic lipid accumulation (2020)
  • Author(s): Tanaka Miyako
  • Journal Title: Endocrine Journal Volume: 67 Issue: 2 Pages: 107-111
  • DOI: 10.1507/endocrj.EJ19-0417
  • NAID: 130007802887
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed
• [Journal Article] Microneedle‐Array Patch Fabricated with Enzyme‐Free Polymeric Components Capable of On‐Demand Insulin Delivery (2018)
  • Author(s): Chen Siyuan、Matsumoto Hiroko、Moro‐oka Yuki、Tanaka Miyako、Miyahara Yuji、Suganami Takayoshi、Matsumoto Akira
  • Journal Title: Advanced Functional Materials Volume: - Issue: 7 Pages: 1807369-1807369
  • DOI: 10.1002/adfm.201807369
  • Peer Reviewed
• [Presentation] Role of Mincle in sterile inflammation (2021)
  • Author(s): 田中 都，小川佳宏，菅波孝祥
  • Organizer: 第85回日本循環器学会学術集会
  • Invited
• [Presentation] 組織リモデリングとMincle (2021)
  • Author(s): 田中 都，小川佳宏，菅波孝祥
  • Organizer: 第41回日本肥満学会
  • Invited
• [Presentation] C-type lectin Mincle mediates cell death-triggered sustained inflammation after acute kidney injury in mice (2020)
  • Author(s): Miyako Tanaka, Marie Saka-Tanaka, Kozue Ochi, Kumiko Fujieda, Hiro Ishihara, Naotake Tsuboi, Shoichi Maruyama, Yoshihiro Ogawa, Takayoshi Suganami
  • Organizer: 2020 Keystone Symposia for the meeting on Fibrosis and Tissue Repair: From Molecules and Mechanics to Therapeutic Approaches
  • Int'l Joint Research
• [Presentation] C-type lectin Mincle mediates cell death-triggered sustained inflammation (2020)
  • Author(s): Miyako Tanaka，Yoshihiro Ogawa，Takayoshi Suganami
  • Organizer: 第97回日本生理学会大会
  • Invited
• [Presentation] 新規死細胞センサー Mincleを介するマクロファージ・死細胞ネットワークと炎症遷延化機構 (2019)
  • Author(s): 田中 都，小川佳宏，菅波孝祥
  • Organizer: 第42回日本分子生物学会年会
  • Invited
• [Presentation] 新規死細胞センサーMincleの可能性を探る (2019)
  • Author(s): 田中 都，小川佳宏，菅波孝祥
  • Organizer: 第37回内分泌代謝学サマーセミナー
  • Invited
• [Presentation] 細胞間クロストーク・臓器間ネットワークに着目した肥満・糖尿病の病態解明 (2019)
  • Author(s): 田中 都
  • Organizer: 第92回日本内分泌学会学術総会
  • Invited
• [Presentation] Synthetic “smart gel” provides glucose-responsive insulin delivery in diabetic mice (2019)
  • Author(s): Miyako Tanaka, Akira Matsumoto, Hiroko Matsumoto, Kozue Ochi, Yuki Moro-oka, Hirohito Kuwata, Ibuki Shirakawa, Taiki Miyazawa, Yuji Miyahara, Takayoshi Suganami
  • Organizer: 2019 Keystone Symposia for the meeting on Obesity and Adipose Tissue Biology
  • Int'l Joint Research
• [Presentation] C-type lectin Mincle accelerates renal ischemia-reperfusion injury (2018)
  • Author(s): Miyako Tanaka, Marie Saka-Tanaka, Naotake Tsuboi, Shoichi Maruyama, Takayoshi Suganami
  • Organizer: The American Society of Nephrology Kidney Week 2018
  • Int'l Joint Research
• [Presentation] アディポカインによる炎症・免疫制御 (2018)
  • Author(s): 田中 都，蜂屋瑠見，小川佳宏，菅波孝祥
  • Organizer: 第18回日本抗加齢医学会総会
  • Invited
• [Presentation] C-type lectin Mincle accelerates renal ischemia-reperfusion injury (2018)
  • Author(s): Miyako Tanaka, Marie Saka-Tanaka, Kozue Ochi, Kumiko Fujieda, Hiro Kohda, Naotake Tsuboi, Shoichi Maruyama, Tomofumi Miyamoto, Sho Yamasaki, Yoshihiro Ogawa, Takayoshi Suganami
  • Organizer: Australia-Japan Meeting on Cell Death
  • Int'l Joint Research
• [Presentation] 緑豆タンパク質の生活習慣病予防効果 -脂肪肝，脂肪組織炎症に着目して- (2018)
  • Author(s): 田中 都，越智 梢，渡辺亜希子，木村久美，橘 伸彦，井上 啓，菅波孝祥
  • Organizer: 第72回 日本栄養・食糧学会大会
• [Presentation] 急性腎障害における新規細胞死センサーMincleの病態生理的意義 (2018)
  • Author(s): 田中 都，坂（田中）まりえ，越智 梢，神田 容，藤枝久美子，山﨑 晶，坪井直毅，丸山彰一，小川佳宏，菅波孝祥
  • Organizer: 第22回心血管内分泌代謝学会学術集会
• [Presentation] グルコース応答性スマートゲルを用いた新規インスリンデバイスの開発 (2018)
  • Author(s): 田中 都，桒田博仁，越智 梢，松本裕子，後藤沙也香，白川伊吹，宮原裕二，石井 均，小川佳宏，松元 亮，菅波孝祥
  • Organizer: 第91回日本内分泌学会学術総会
• [Patent(Industrial Property Rights)] 温度耐性型糖応答性ゲル (2018)
  • Inventor(s): 菅波孝祥、田中 都、松元 亮、松本裕子、諸岡由佳、宮原裕二
  • Industrial Property Rights Holder: 菅波孝祥、田中 都、松元 亮、松本裕子、諸岡由佳、宮原裕二
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
• [Patent(Industrial Property Rights)] 非アルコール性脂肪肝炎及び／又は肝臓がんのモデル動物の製造方法 (2018)
  • Inventor(s): 菅波孝祥、田中 都、越智 梢
  • Industrial Property Rights Holder: 菅波孝祥、田中 都、越智 梢
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018