The regulation of energy metabolism by brown-adipokine

• Project/Area Number: 24659113
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General pharmacology
• Research Institution: Kanazawa University
• Principal Investigator: HINOI Eiichi 金沢大学, 薬学系, 准教授 (70360865)
• Co-Investigator(Renkei-kenkyūsha): SAKURAI Takeshi 金沢大学, 医学系, 教授 (60251055)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: brown adipocyte / obesity / energy expenditure / 褐色脂肪細胞 / 白色脂肪細胞 / GDF5 / 肥満 / 脂肪細胞

Research Abstract

Although the growth differentiate factor 5 (GDF5) has been implicated in skeletal development in mammal, little attention has been paid to the functionality in adipogenesis and energy homeostasis. Here, we show a critical role of the GDF5 in regulating both brown adipogenesis and whole-body energy expenditure. Transgenic mice overexpressing GDF5 in adipose tissues not only showed a lean phenotype but protection against high fat diet-induced obesity due to increased energy expenditure. On the contrary, mutant mice harboring dominant-negative form of GDF5 have impaired energy expenditure and thermogenesis on obesogenic condition. GDF5 activated brown adipogenesis through bone morphological protein receptor (BMPR) pathway. Taken together, these findings demonstrate that GDF5/BMPR pathway regulates brown adipogenesis and energy homeostasis and suggest that modulation of this pathway might be a plausible strategy for obesity and metabolic dysfunctions.

Research Products

• [Journal Article] Growth differentiation factor-5 promotes brown adipogenesis in systemic energy expenditure (2014)
  • Author(s): Eiichi Hinoi, Yukari Nakamura, Saya Takada, Hiroyuki Fujita, Takashi Iezaki, Syota Hashizume, Satoshi Takahashi, Yoshiaki Odaka, Takumi Watanabe and Yukio Yoneda
  • Journal Title: Diabetes Volume: 63 Issue: 1 Pages: 162-175
  • DOI: 10.2337/db13-0808
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Repression of adipogenesis through promotion of Wnt/ß-catenin signaling by TIS7 up-regulated in adipocytes under hypoxia. (2013)
  • Author(s): Yukari Nakamura, Eiichi Hinoi, Takashi Iezaki, Saya Takada, Syota Hashizume, Yoshifumi Takahata, Emiko Tsuruta, Satoshi Takahashi and Yukio Yoneda *Equally contributed.
  • Journal Title: BBA Mol, Basis Dis Volume: 1832 Issue: 8 Pages: 1117-1128
  • DOI: 10.1016/j.bbadis.2013.03.010
  • Peer Reviewed
• [Journal Article] The transcription factor paired box-5 promotes osteoblastogenesis through direct induction of Osterix and Osteocalcin (2012)
  • Author(s): Hinoi, E., Nakatani, E., Yamamoto, T., Iezaki, T., Takahata, Y., Fujita, H., Ishiura, R., Takamori, M. and Yoneda, Y
  • Journal Title: J. Bone Miner. Res Volume: 27 Issue: 12 Pages: 2526-34
  • DOI: 10.1002/jbmr.1708
  • Peer Reviewed
• [Journal Article] Positive regulation of osteoclastic differentiation by growth differentiation factor-15 up-regulated in osteocytic cells under hypoxia (2012)
  • Author(s): Eiichi Hinoi, Hiroki Ochi, Takeshi Takarada, Eri Nakatani, Takashi Iezaki, Hiroko Nakajima, Hiroyuki Fujita, Yoshifumi Takahata, Shinya Hidano, Takashi Kobayashi, Shu Takeda, Yukio Yoneda
  • Journal Title: J Bone Miner Res Volume: 4 Issue: 4 Pages: 938-949
  • DOI: 10.1002/jbmr.1538
  • Peer Reviewed
• [Presentation] 骨組織による糖代謝調節機構 (2012)
  • Author(s): 檜井栄一
  • Organizer: 第1回糖尿病と新しい合併症を考える会～糖尿病と骨～
  • Place of Presentation: 京成ホテルミラマーレ(千葉県)
  • Year and Date: 2012-09-07
• [Presentation] 骨組織による糖代謝調節機構
  • Author(s): 檜井栄一
  • Organizer: 第1回糖尿病と新しい合併症を考える会～糖尿病と骨～
  • Place of Presentation: 京成ホテルミラマーレ（千葉）
  • Invited
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~yakubutu/index.html