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Zic1 mRNA 在急性冷暴露小鼠的皮下脂肪中短暂上调。

Zic1 mRNA is transiently upregulated in subcutaneous fat of acutely cold-exposed mice.

机构信息

Department of Experimental and Clinical Medicine, Center of Obesity, University of Ancona (Politecnica delle Marche), Ancona, Marche, Italy.

School of Pharmacy, Department of Biochemistry and Molecular Biology, University of Camerino, Camerino, Macerata, Italy.

出版信息

J Cell Physiol. 2019 Mar;234(3):2031-2036. doi: 10.1002/jcp.27301. Epub 2018 Oct 20.

Abstract

In the mammalian adipose organ cold exposure not only activates typical brown adipose tissue, but also induces browning, that is the formation of thermogenic multilocular adipocytes in white, or predominantly white, adipose depots such as subcutaneous fat. Unlike typical brown adipocytes, newly formed thermogenic adipocytes have been reported not to express the gene zinc finger of the cerebellum 1 (Zic1). Here, a time course approach enabled us to document a significant increase in Zic1 messenger RNA in inguinal subcutaneous fat from acutely (24 hr) cold-exposed mice, which was paralleled by an increase in multilocular and paucilocular uncoupling protein 1-positive adipocytes and in parenchymal noradrenergic innervation. This transient, depot-specific molecular signature was associated not to Zic1 promoter demethylation, but to chromatin remodeling through an H3K9me3 histone modification. These findings challenge the notion that Zic1 is exclusively expressed by typical brown adipocytes and suggest its involvement in brown adipocyte precursor differentiation and/or white-to-brown adipocyte transdifferentiation.

摘要

在哺乳动物的脂肪组织中,寒冷暴露不仅会激活典型的棕色脂肪组织,还会诱导褐色化,即在白色或主要为白色的脂肪组织(如皮下脂肪)中形成产热的多房脂肪细胞。与典型的棕色脂肪细胞不同,新形成的产热脂肪细胞据报道不表达小脑 1 锌指基因(Zic1)。在这里,我们采用时间过程方法记录了急性(24 小时)冷暴露小鼠腹股沟皮下脂肪中 Zic1 信使 RNA 的显著增加,这与多房和少房解偶联蛋白 1 阳性脂肪细胞以及实质去甲肾上腺素能神经支配的增加相平行。这种短暂的、特定于脂肪库的分子特征与 Zic1 启动子去甲基化无关,而是通过 H3K9me3 组蛋白修饰进行染色质重塑。这些发现挑战了 Zic1 仅由典型棕色脂肪细胞表达的观点,并表明其参与棕色脂肪前体细胞的分化和/或白色脂肪向棕色脂肪的转分化。

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