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.

生长分化因子5（growth differentiation factor 5，GDF 5）在哺乳动物骨骼发育过程中发挥重要作用，但其在脂肪形成和能量平衡中的作用却很少受到关注。在这里，我们展示了GDF 5在调节棕色脂肪形成和全身能量消耗方面的关键作用。在脂肪组织中过表达GDF 5的转基因小鼠不仅表现出瘦的表型，而且由于能量消耗增加而防止高脂肪饮食诱导的肥胖。相反，携带GDF 5显性阴性形式的突变小鼠在致肥胖条件下具有受损的能量消耗和产热。GDF 5通过骨形态蛋白受体（BMPR）途径激活棕色脂肪细胞的形成。综上所述，这些发现表明GDF 5/BMPR途径调节棕色脂肪形成和能量稳态，并表明调节该途径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

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

Positive Regulation of Osteoclastic Differentiation by Growth Differentiation Factor 15 Upregulated in Osteocytic Cells Under Hypoxia

• DOI: 10.1002/jbmr.1538
• 发表时间: 2012-04-01
• 期刊: JOURNAL OF BONE AND MINERAL RESEARCH
• 影响因子: 6.2
• 作者: Hinoi, Eiichi;Ochi, Hiroki;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