New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure.
New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure.
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DOI：
10.1038/nature07221
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发表时间：
2008-08-21
期刊：
影响因子：
64.8
通讯作者：
Kahn, C. Ronald
中科院分区：
文献类型：
--
作者：
Tseng, Yu-Hua;Kokkotou, Efi;Schulz, Tim J.;Huang, Tian Lian;Winnay, Jonathon N.;Taniguchi, Cullen M.;Tran, Thien T.;Suzuki, Ryo;Espinoza, Daniel O.;Yamamoto, Yuji;Ahrens, Molly J.;Dudley, Andrew T.;Norris, Andrew W.;Kulkarni, Rohit N.;Kahn, C. Ronald
脂肪组织是调节能量平衡的中心。哺乳动物体内存在两种功能不同的脂肪：白色脂肪组织(Wat)和棕色脂肪组织(BAT)，白色脂肪组织是储存甘油三酯的主要部位，棕色脂肪组织专门负责能量消耗，可以抵消肥胖。决定白色和棕色脂肪组织发育命运和功能的因素仍然知之甚少。在这里，我们证明了尽管骨形态发生蛋白(BMP)家族的一些成员支持白色脂肪细胞分化，但BMP-7即使在缺乏正常所需的激素诱导鸡尾酒的情况下也能单独促进棕色前脂肪细胞的分化。骨形态发生蛋白-7激活了棕色脂肪形成的完整程序，包括诱导棕色脂肪早期调节因子PrDM16和PGC-1(PPARγ辅活化子-1)α，增加棕色脂肪定义标记解偶联蛋白-1和成脂转录因子过氧化物酶体增殖物激活受体γ和CCAAT/增强子结合蛋白(C/EBPs)的表达，以及通过p38 MAP激酶和PGC-1依赖的途径实现线粒体的生物形成。此外，BMP-7触发间充质祖细胞向棕色脂肪细胞谱系的承诺，将这些细胞移植到裸鼠体内会导致以棕色脂肪细胞为主的脂肪组织的发育。BMP-7基因敲除的胚胎明显缺乏棕色脂肪，几乎完全缺乏UCP-1蛋白。腺病毒介导的BMP-7在小鼠体内的表达导致棕色脂肪质量显著增加，但不是白色脂肪质量，并导致能量消耗增加和体重增加减少。这些数据揭示了BMP-7在体内和体外促进棕色脂肪细胞分化和产热方面的重要作用，并为肥胖症的治疗提供了一种潜在的新的治疗方法。
Adipose tissue is central to the regulation of energy balance. Two functionally different types of fat are present in mammals: white adipose tissue (WAT), the primary site of triglyceride storage, and brown adipose tissue (BAT), which is specialized in energy expenditure and can counteract obesity. Factors that specify the developmental fate and function of white and brown adipose tissue remain poorly understood. Here, we demonstrate that while some members of the family of bone morphogenetic proteins (BMP) support white adipocyte differentiation, BMP-7 singularly promotes differentiation of brown preadipocytes even in the absence of the normally required hormonal induction cocktail. BMP-7 activates a full program of brown adipogenesis including induction of early regulators of brown fat fate PRDM16 and PGC-1 (PPARγ coactivator-1) α, increased expression of brown fat defining marker uncoupling protein-1 (UCP-1) and adipogenic transcription factors peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding proteins (C/EBPs), and mitochondrial biogenesis via a p38 MAP kinase and PGC-1 dependent pathway. Moreover, BMP-7 triggers commitment of mesenchymal progenitor cells to a brown adipocyte lineage, and implantation of these cells into nude mice results in development of adipose tissue containing mostly brown adipocytes. BMP-7 knockout embryos show a marked paucity of brown fat and near complete absence of UCP-1 protein. Adenoviral-mediated expression of BMP-7 in mice results in a significant increase in brown, but not white, fat mass and leads to an increase in energy expenditure and reduced weight gain. These data reveal an important role of BMP-7 in promoting brown adipocyte differentiation and thermogenesis in vivo and in vitro, and provide a potential novel therapeutic approach for the treatment of obesity.
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影响因子：
21.3
作者：
Tseng, YH;Butte, AJ;Kahn, CR
通讯作者：
Kahn, CR
影响因子：
64.5
作者：
Puigserver, P;Wu, ZD;Spiegelman, BM
通讯作者：
Spiegelman, BM
影响因子：
29
作者：
Seale, Patrick;Kajimura, Shingo;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
Osf2/Cbfa1：成骨细胞分化的转录激活因子
影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G
影响因子：
11.8
作者：
Jin, WZ;Takagi, T;Ishii, S
通讯作者：
Ishii, S