BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis
BMP4-mediated brown fat-like changes in white adipose tissue alter glucose and energy homeostasis
复制标题
BMP4介导的白色脂肪组织中的棕色脂肪样变化改变了葡萄糖和能量稳态
DOI：
10.1073/pnas.1215236110
复制
发表时间：
2013-02-26
影响因子：
11.1
通讯作者：
Tang, Qi-Qun
中科院分区：
文献类型：
--
作者：
Qian, Shu-Wen;Tang, Yan;Tang, Qi-Qun
白色脂肪组织（WAT）脂肪细胞中骨形态发生蛋白4 （BMP4）的表达产生具有棕色脂肪特征的“白色脂肪细胞”，并导致肥胖及其代谢并发症的减少。虽然已知BMP4通过产生具有前脂肪细胞特征的细胞诱导多能干细胞向脂肪细胞谱系的转化，但其对成熟白色脂肪细胞表型和功能的影响尚不清楚。在小鼠白色脂肪细胞中强制表达BMP4转基因会导致WAT质量和白色脂肪细胞大小的减少，同时白色脂肪细胞类型的数量增加，其棕色脂肪细胞的特征与米色或白白色脂肪细胞相似。这些变化与能量消耗的增加、胰岛素敏感性的提高以及防止饮食引起的肥胖和糖尿病密切相关。相反，bmp4缺陷小鼠表现出白色脂肪细胞形态增大和胰岛素敏感性受损。我们发现过氧化物酶体增殖体激活受体γ辅助激活因子1- α (PGC1 α)是WAT中这些棕色脂肪样变化所需的BMP信号传导的靶标。BMP4对WAT的影响似乎延伸到人类脂肪组织，因为WAT中BMP4的表达水平与体重指数呈负相关。这些发现为BMP4通过影响WAT的发展而改变胰岛素敏感性提供了遗传和代谢基础。
Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1 alpha) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4's role in altering insulin sensitivity by affecting WAT development.