Adipocytes play crucial roles in the control of whole‐body energy homeostasis. Differentiation and functions of the adipocytes are regulated by various transcription factors. Zfat (zinc‐finger protein with AT‐hook) is a transcriptional regulator that controls messenger RNA expression of specific genes through binding to their transcription start sites. Here we report important roles of Zfat in the adipocytes. We establish inducible Zfat‐knockout (Zfat iKO) mice where treatment with tamoxifen causes a marked reduction in Zfat expression in various tissues. Tamoxifen treatment of Zfat iKO mice reduces the white adipose tissues (WATs) mass, accompanied by the decreased triglyceride levels. Zfat is expressed in both the adipose‐derived stem cells (ADSCs) and mature adipocytes in the WATs. In ex vivo assays of the mature adipocytes differentiated from the Zfat iKO ADSCs, loss of Zfat in the mature adipocytes reduces the triglyceride levels, suggesting cell autonomous roles of Zfat in the maintenance of the mature adipocytes. Furthermore, we identify the Atg13, Brf1, Psmc3, and Timm22 genes as Zfat‐target genes in the mature adipocytes. In contrast, loss of Zfat in the ADSCs impairs adipocyte differentiation with the decreased expression of C/EBPα and adiponectin. Thus, we propose that Zfat plays crucial roles in maintenance and differentiation of the adipocytes.

中文翻译：

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转录调节因子 Zfat 对脂肪细胞的维持和分化至关重要

脂肪细胞在控制全身能量稳态方面起着至关重要的作用。脂肪细胞的分化和功能受各种转录因子的调控。Zfat（带 AT 钩的锌指蛋白）是一种转录调节因子，通过与特定基因的转录起始位点结合来控制特定基因的信使 RNA 表达。在这里，我们报告了 Zfat 在脂肪细胞中的重要作用。我们建立诱导型Zfat‐敲除 (Zfat iKO) 小鼠，其中用他莫昔芬治疗导致各种组织中 Zfat 表达显着降低。他莫昔芬治疗 Zfat iKO 小鼠可减少白色脂肪组织 (WAT) 质量，同时降低甘油三酯水平。Zfat 在脂肪干细胞 (ADSC) 和 WAT 中的成熟脂肪细胞中均有表达。在从 Zfat iKO ADSC 分化的成熟脂肪细胞的离体测定中，成熟脂肪细胞中 Zfat 的损失降低了甘油三酯水平，表明 Zfat 在维持成熟脂肪细胞中的细胞自主作用。此外，我们确定了Atg13、Brf1、Psmc3和Timm22基因作为成熟脂肪细胞中的 Zfat 靶基因。相比之下，ADSC 中 Zfat 的损失会随着 C/EBPα 和脂联素的表达降低而损害脂肪细胞分化。因此，我们认为 Zfat 在脂肪细胞的维持和分化中起着至关重要的作用。