The MED1 subunit has been shown to mediate ligand-dependent binding of the Mediator coactivator complex to multiple nuclear receptors, including the adipogenic PPARγ, and to play an essential role in ectopic PPARγ-induced adipogenesis of mouse embryonic fibroblasts. However, the precise roles of MED1, and its various domains, at various stages of adipogenesis and in adipose tissue have been unclear. Here, after establishing requirements for MED1, including specific domains, for differentiation of 3T3L1 cells and both primary white and brown preadipocytes, we used multiple genetic approaches to assess requirements for MED1 in adipocyte formation, maintenance, and function in mice. We show that MED1 is indeed essential for the differentiation and/or function of both brown and white adipocytes, as its absence in these cells leads to, respectively, defective brown fat function and lipodystrophy. This work establishes MED1 as an essential transcriptional coactivator that ensures homeostatic functions of adipocytes.

中文翻译：

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转录共激活因子 MED1 在小鼠脂肪组织形成和功能中的关键作用

MED1 亚基已显示介导 Mediator 共激活剂复合物与多种核受体（包括脂肪生成 PPARγ）的配体依赖性结合，并在异位 PPARγ 诱导的小鼠胚胎成纤维细胞脂肪生成中发挥重要作用。然而，MED1 及其各种结构域在脂肪生成的各个阶段和脂肪组织中的确切作用尚不清楚。在这里，在确定了 MED1 的要求（包括特定域）后，用于分化 3T3L1 细胞以及原代白色和棕色前脂肪细胞，我们使用多种遗传方法来评估 MED1 在小鼠脂肪细胞形成、维持和功能方面的要求。我们表明 MED1 对于棕色和白色脂肪细胞的分化和/或功能确实是必不可少的，因为它们在这些细胞中的缺失分别导致，棕色脂肪功能缺陷和脂肪代谢障碍。这项工作将 MED1 确立为一种必需的转录共激活因子，可确保脂肪细胞的稳态功能。