The regulation of energy metabolism by brown-adipokine

2013 Fiscal Year Final Research Report

• 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
• Keywords: brown adipocyte / obesity / energy expenditure

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): Hinoi, E., Nakamura, Y., Takada, S., Fujita, H., Iezaki, T., Hashizume, S., Takahashi, S., Odaka, Y., Watanabe, T. and Yoneda Y
  • Journal Title: Diabetes Volume: 63 Pages: 162-75
  • DOI: 10.2337/db13-0808
  • Peer Reviewed
• [Journal Article] Repression of adipogenesis through promotion of Wnt/ß-catenin signaling by TIS7 up-regulated in adipocytes under hypoxia (2013)
  • Author(s): Nakamura, Y., Hinoi, E., Iezaki, T., Takada, S., Hashizume, S., Takahata, Y., Tsuruta, E., Takahashi, S. and Yoneda, Y
  • Journal Title: Biochim. Biophys. Acta. Mol. Basis Dis. Volume: 1832 Pages: 1117-28
  • 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 Pages: 2526-34
  • DOI: 10.1002/jbmr.1708
  • 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
• [Remarks]
  • URL: http://www.p.kanazawa-u.ac.jp/~yakubutu/index.html