The regulation of energy metabolism by brown-adipokine

棕色脂肪因子对能量代谢的调节

• 批准号: 24659113
• 负责人: HINOI Eiichi
• 金额: $ 2.5万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Challenging Exploratory Research
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-24659113/
• 关键词: brown adipocyte; obesity; energy expenditure; 褐色脂肪細胞; 白色脂肪細胞; GDF5; 肥満; 脂肪細胞

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.

尽管生长区分因子5（GDF5）与哺乳动物的骨骼发育有关，但对脂肪生成和能量稳态的功能几乎没有关注。在这里，我们在调节棕色脂肪形成和全身能量消耗方面显示了GDF5的​​关键作用。脂肪组织中过表达GDF5的​​转基因小鼠不仅显示出瘦的表型，而且还可以保护高脂饮食诱导的高脂肪饮食引起的肥胖，这是由于能量消耗增加而导致的。相反，具有主要阴性形式的GDF5的​​突变小鼠在肥胖状态下的能量消耗和热发生受损。 GDF5通过骨形态蛋白受体（BMPR）途径激活了棕色脂肪形成。综上所述，这些发现表明，GDF5/BMPR途径调节棕色的脂肪生成和能量稳态，并表明对该途径的调节可能是肥胖和代谢功能障碍的合理策略。

项目成果

The Transcription Factor Paired Box-5 Promotes Osteoblastogenesis Through Direct Induction of Osterix and Osteocalcin

• DOI: 10.1002/jbmr.1708
• 发表时间: 2012-12-01
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Hinoi, Eiichi;Nakatani, Eri;Yoneda, Yukio
• 通讯作者: Yoneda, Yukio

Growth Differentiation Factor-5 Promotes Brown Adipogenesis in Systemic Energy Expenditure

• DOI: 10.2337/db13-0808
• 发表时间: 2014-01-01
• 期刊: DIABETES
• 影响因子: 7.7
• 作者: Hinoi, Eiichi;Nakamura, Yukari;Yoneda, Yukio
• 通讯作者: Yoneda, Yukio

骨組織による糖代謝調節機構

骨组织对葡萄糖代谢的调节机制

• 发表时间: 2012
• 作者: Eiichi Hinoi;Hiroki Ochi;Takeshi Takarada;Eri Nakatani;Takashi Iezaki;Hiroko Nakajima;Hiroyuki Fujita;Yoshifumi Takahata;Shinya Hidano;Takashi Kobayashi;Shu Takeda;Yukio Yoneda;檜井栄一
• 通讯作者: 檜井栄一