Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1α
Rb and p107 regulate preadipocyte differentiation into white versus brown fat through repression of PGC-1α
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DOI：
10.1016/j.cmet.2005.10.002
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发表时间：
2005-11-01
期刊：
影响因子：
29
通讯作者：
Rudnicki, MA
中科院分区：
文献类型：
--
作者：
Scimè, A;Grenier, G;Rudnicki, MA
Rb家族，Rb，p107和p130，在细胞周期控制和细胞分化中起重要作用，并且Rb已被建议调节脂肪细胞分化。我们在这里报告，缺乏p107的小鼠表现出均匀的替代白色脂肪组织（WAT）与棕色脂肪组织（BAT）。突变WAT贮库含有多房脂肪细胞，其表达升高水平的BAT典型的PGC-1 α和UCP-1。来自p107（-1-）小鼠的WAT含有显著增加的成脂前体，其显示pRb表达下调。与成人脂肪细胞分化需要pRb的假设一致，Cre介导的成人原代前脂肪细胞中Rb的缺失阻断了它们向白色脂肪细胞的分化。重要的是，观察到pRb结合PGC-1 α启动子并抑制转录。因此，p107和pRb调节PGC-1 α的表达，以控制脂肪组织中假定的成体祖细胞的共同库分化为白色和棕色脂肪细胞之间的转换。
The Rb family, Rb, p107, and p130, play important roles in cell cycle control and cellular differentiation, and Rb has been suggested to regulate adipocyte differentiation. We report here that mice lacking p107 displayed a uniform replacement of white adipose tissue (WAT) with brown adipose tissue (BAT). Mutant WAT depots contained mutilocular adipocytes that expressed elevated levels of PGC-1 alpha and UCP-1 typical of BAT. WAT from p107(-1-) mice contained markedly elevated numbers of adipogenic precursors that displayed downregulated expression of pRb. Consistent with the hypothesis that pRb is required for adult adipocyte differentiation, Cre-mediated deletion of Rb in adult primary preadipocytes blocked their differentiation into white adipocytes. Importantly, pRb was observed to bind the PGC-1 alpha promoter and repress transcription. Therefore, p107 and pRb regulate PGC-1 alpha expression to control the switch between white and brown adipocyte differentiation from a common pool of presumptive adult progenitors in fat tissue.