Elucidation of Regulatory Mechanism of Brown Adipocyte Differentiation and Glucose, Lipid and Energy Metabolism by NFIA

• Project/Area Number: 17K09818
• 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 Tokyo
• Principal Investigator: Waki Hironori 東京大学, 医学部附属病院, 准教授 (00466765)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 褐色脂肪細胞 / 転写 / 遺伝子 / 分化 / 肥満 / 糖尿病 / トランスジェニック / ノックアウト / 脂肪細胞 / 脂質

Outline of Final Research Achievements

Brown adipose tissue has attracted attention as a therapeutic target for obesity. We discovered that a transcription factor NFIA plays an important role in the regulation of brown-adipocyte-specific gene expression. NFIA knockout mice die within a few weeks after birth due to neurological deficit. By creating adipose-tissue-specific NFIA knockout mice and transgenic mice and by studying regulatory mechanism of NFIA, we elucidated NFIA's role in gene regulation and systemic enegery metabolism and its relation to environment.

Academic Significance and Societal Importance of the Research Achievements

脂肪細胞におけるこれまでのNFIAの知見に加えて、成体の全身のエネルギー代謝と環境因子との関連におけるNFIAの役割を明らかなった点で、肥満やメタボリックシンドローム、２型糖尿病などの疾患の治療に役立つ可能性が示唆された。

Research Products

• [Journal Article] 脂肪細胞における転写・エピゲノム制御と糖・脂質エネルギー代謝における意義 (2019)
  • Author(s): 脇 裕典
  • Journal Title: Cardio-Renal Diabetes Volume: 8 Pages: 116-121
• [Journal Article] 脂肪細胞の褐色化のメカニズム：新規治療への応用 (2019)
  • Author(s): 脇 裕典
  • Journal Title: 糖尿病最新の治療2019-2021 Volume: . Pages: 44-47
• [Journal Article] 褐色脂肪細胞のエピゲノム制御におけるNFIAの役割 (2018)
  • Author(s): 脇 裕典
  • Journal Title: 糖尿病学2018 Volume: .
• [Journal Article] 褐色脂肪組織と肥満症 (2018)
  • Author(s): 脇 裕典
  • Journal Title: Medical Practice Volume: 35(2) Pages: 269-272
• [Journal Article] NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program. (2017)
  • Author(s): Hiraike Y, Waki H, Yu J, Nakamura M, Miyake K, Nagano G, Nakaki R, Suzuki K, Kobayashi H, Yamamoto S, Sun W, Aoyama T, Hirota Y, Ohno H, Oki K, Yoneda M, White AP, Tseng YH, Cypess AM, Larsen TJ, Jespersen NZ, Scheele C, Tsutsumi S, Aburatani H, Yamauchi T, Kadowaki T
  • Journal Title: Nature cell biology Volume: 19(9) Issue: 9 Pages: 1081-1092
  • DOI: 10.1038/ncb3590
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Transcriptional regulation of brown and beige adipocyte differentiation (2019)
  • Author(s): Hironori Waki
  • Organizer: APDO Symposium 2019, Asia-Pacific Diabetes and Obesity Study Group Annual Meeting
  • Int'l Joint Research / Invited
• [Presentation] Transcriptional regulation of brown and beige adipocyte differentiation (2019)
  • Author(s): Hironori Waki
  • Organizer: 2019 International Congress on Obesity and Metabolic Syndrome & Asia-Oceania Conference on Obesity (ICOMES & AOCO 2019)
  • Int'l Joint Research / Invited
• [Presentation] 褐色脂肪細胞のエピゲノム制御と肥満症における意義 (2019)
  • Author(s): 脇 裕典
  • Organizer: 第24回アディポサイエンス・シンポジウム
  • Int'l Joint Research / Invited
• [Presentation] 肥満と健康の最新の話題 ～ 注目される褐色脂肪細胞とは (2019)
  • Author(s): 脇 裕典
  • Organizer: 世界糖尿病デー記念事業 第7回 世界糖尿病デー in たじみ
  • Int'l Joint Research / Invited
• [Presentation] Nuclear Factor I-Aによる褐色脂肪特異的 転写プログラムとエネルギー代謝の制御 (2019)
  • Author(s): 脇 裕典
  • Organizer: 第40回 日本肥満学会 第37回 日本肥満症治療学会学術集会 シンポジウム17 肥満と脂肪組織リモデリング
  • Int'l Joint Research / Invited
• [Presentation] 褐色脂肪細胞のエピゲノム制御と肥満症における意義 (2019)
  • Author(s): 脇裕典
  • Organizer: 第53回糖尿病学の進歩
• [Presentation] 褐色脂肪細胞のエピゲノム制御と全身の代謝 (2019)
  • Author(s): 脇裕典
  • Organizer: 第33回日本糖尿病・肥満動物学会年次学術集会
• [Presentation] Exploring and characterizing the novel target genes of NFIA in brown adipocytes. (2019)
  • Author(s): Misato Oguchi, Hironori Waki, Yuta Hiraike, Takahito Wada, Kaede Saito, Shin-ichi Tamaru, Masahiro Nakamura, Toshimasa Yamauchi, Takashi Kadowaki
  • Organizer: International Symposium on Epigenome 2019
• [Presentation] NFIAはPRDM16と独立にかつ協調して褐色脂肪細胞分化を制御する (2018)
  • Author(s): 大口弥里、平池勇雄、脇裕典、和田孝人、山内敏正、門脇孝
  • Organizer: 第61回日本糖尿病学会
• [Presentation] シンポジウム１「褐色脂肪特異的な転写制御とゲノム・エピゲノム」 (2018)
  • Author(s): 大口弥里、平池勇雄、脇裕典、和田孝人、山内敏正、門脇孝
  • Organizer: 第36回日本肥満症治療学会学術集会
• [Presentation] NFIAはPRDM16と独立にかつ協調して褐色脂肪細胞分化を制御する (2018)
  • Author(s): 大口弥里、平池勇雄、脇裕典、和田孝人、山内敏正、門脇孝
  • Organizer: 第23回アディポサイエンス・シンポジウム
• [Presentation] NFIAはPRDM16と独立にかつ協調して褐色脂肪細胞分化を制御する (2018)
  • Author(s): 大口弥里、平池勇雄、脇裕典、和田孝人、山内敏正、門脇孝
  • Organizer: 第39回日本肥満学会
• [Presentation] NFIA Co-Localizes with PPARgamma and Activates the Cell-Type-Specific Enhancers to Control the Brown Fat Gene Program. (2018)
  • Author(s): Yuta Hiraike, Hironori Waki, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi and Takashi Kadowaki
  • Organizer: American Diabetes Association's 78th Scientific Sessions
• [Presentation] Transcriptional Regulation of Brown Adipocytes and Its Implication for Obesity in Humans. (2018)
  • Author(s): Hironori Waki
  • Organizer: APDO Symposium 2018, Asia-Pacific Diabetes and Obesity Study Group Joint with the 39th Annual Meeting of Japan Society for the Study of Obesity
• [Presentation] Transcriptional Regulation of Brown Adipocytes and Its Implication for Humans (2018)
  • Author(s): Hironori Waki
  • Organizer: The 4th IMCR Symposium on Endocrine and Metabolism: At the Cutting Edge of Metabolic Regulation Research
• [Presentation] NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program. (2018)
  • Author(s): Yuta Hiraike, Hironori Waki, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi1 and Takashi Kadowaki
  • Organizer: Keystone Symposia, Bioenergetics and Metabolic Disease (J4) (Keystone, USA, 2018.1.21-25)
  • Int'l Joint Research
• [Presentation] 臨床医が知っておくべき糖尿病の基礎～糖尿病とエピゲノム (2018)
  • Author(s): 脇裕典
  • Organizer: 第52回糖尿病学の進歩（2018年3月 福岡）
  • Invited
• [Presentation] Co-Localization of NFIA and PPARγ Controls the Brown Fat Gene Program (2017)
  • Author(s): Hironori Waki
  • Organizer: Translational and Therapeutic Perspectives of Brown Adipose (Copenhagen, Denmark)
  • Int'l Joint Research
• [Presentation] Controls the Brown Fat Gene Program by Co-Localizing with PPARgamma at Cell-Type-Specific Enhancers (2017)
  • Author(s): Yuta Hiraike, Hironori Waki, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi, Takashi Kadowaki
  • Organizer: 3rd Korea-Japan Diabetes Forum in conjunction with the30th Spring Congress of Korean Diabetes Association (Busan, Korea, 2017.5)
  • Int'l Joint Research
• [Presentation] NFIA Controls the Brown Fat Gene Program by Co-Localizing with PPARgamma at Cell Type-Specific Enhancers (2017)
  • Author(s): Yuta Hiraike, Hironori Waki, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi, Takashi Kadowaki
  • Organizer: 77th Scientific Sessions of the American Diabetes Association（San Diego, USA, 2017.6. 9-13)
  • Int'l Joint Research
• [Presentation] NFIA Controls the Brown Fat Gene Program by Co-Localizing with PPARgamma at Cell Type-Specific Enhancers (2017)
  • Author(s): Yuta Hiraike, Hironori Waki, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi, Takashi Kadowaki:
  • Organizer: The 9th Asia-Oceania Conference on Obesity（Adelaide, Australia, 2017.10）
  • Int'l Joint Research
• [Presentation] NFIAは褐色脂肪遺伝子エンハンサーにおいてPPARγと共局在することで褐色脂肪の遺伝子プログラムを制御する (2017)
  • Author(s): 平池勇雄、脇裕典、于静、中村正裕、三宅加奈、鈴木顕、仲木竜、小林博文、和田孝人、孫威、青山倫久、廣田雄輔、長野学、大野晴也、沖健司、米田真康、堤修一、油谷浩幸、山内敏正、門脇孝
  • Organizer: 第60回日本糖尿病学会年次学術集会（2017年5月 名古屋）
• [Presentation] 転写因子NFIAの褐色脂肪分化と筋細胞分化の制御作用ドメインの解析 (2017)
  • Author(s): 三宅加奈、脇裕典、平池勇雄、于静、孫威、青山倫久、山内敏正、門脇孝
  • Organizer: 第60回日本糖尿病学会年次学術集会（2017年5月 名古屋）
• [Presentation] 褐色脂肪細胞におけるエピゲノム制御の分子機構 (2017)
  • Author(s): 脇裕典
  • Organizer: 第67回日本体質医学会総会（2017年9月松山）
  • Invited
• [Presentation] NFIAは褐色脂肪遺伝子エンハンサーでPPARγと共局在し褐色脂肪細胞の遺伝子プログラムを制御する (2017)
  • Author(s): 平池勇雄、脇裕典、于静、中村正裕、三宅加奈、仲木竜、長野学、大野晴也、沖健司、米田真康、堤修一、油谷浩幸、山内敏正、門脇孝
  • Organizer: 第38回日本肥満学会（2017年10月 大阪）
• [Presentation] 転写因子NFIAの褐色脂肪分化と筋細胞分化の制御作用ドメインの解析 (2017)
  • Author(s): 三宅加奈、脇裕典、平池勇雄、于静、青山倫久、山内敏正、門脇孝
  • Organizer: 第38回日本肥満学会（2017年10月 大阪）
• [Presentation] シンポジウム：褐色脂肪細胞におけるエピゲノム制御の分子機構 (2017)
  • Author(s): 脇裕典
  • Organizer: 第38回日本肥満学会（2017年10月 大阪）
  • Invited