Adipose tissue mass is modulated by SLUG (SNAI2)
Adipose tissue mass is modulated by SLUG (SNAI2)
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DOI：
10.1093/hmg/ddm278
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发表时间：
2007-12-01
影响因子：
3.5
通讯作者：
Sanchez-Garcia, Isidro
中科院分区：
文献类型：
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作者：
Antonio Perez-Mancera, Pedro;Bermejo-Rodriguez, Camino;Sanchez-Garcia, Isidro
锌指转录因子SLUG（SNAI 2）触发上皮-间充质转化（EMT），并在发育过程中发挥重要作用。在这里，我们表明，SLUG在人类的白色脂肪组织（WAT）中表达，并且其表达在脂肪细胞分化过程中受到严格控制。Slug缺陷小鼠表现出WAT大小的显著缺陷，而Slug过表达小鼠（Combi-Slug）表现出WAT大小的增加。与体内数据一致，蛞蝓缺陷型小鼠胚胎成纤维细胞（MEFs）显示出体外脂肪生成能力显著降低，并且在Combi-Slug MEFs中存在广泛的脂质积累。在体内和体外脂肪形成基因表达的分析表明，过氧化物酶体增殖物激活因子γ 2（过氧化物酶体增殖物激活因子γ 2）的表达被改变。互补研究拯救了这种表型，表明由Slug诱导的WAT改变是可逆的。我们的研究结果进一步表明，差异组蛋白去乙酰化酶招聘的组织和蛞蝓依赖性的方式的PPAR γ 2启动子。我们的研究结果第一次将脂肪形成与哺乳动物中EMT调节剂的临界水平的要求联系起来。这项工作可能导致开发用于治疗肥胖和/或脂肪代谢障碍患者的靶向药物。
The zinc-finger transcription factor SLUG (SNAI2) triggers epithelial-mesenchymal transitions (EMTs) and plays an important role in the developmental processes. Here, we show that SLUG is expressed in white adipose tissue (WAT) in humans and its expression is tightly controlled during adipocyte differentiation. Slug-deficient mice exhibit a marked deficiency in WAT size, and Slug-overexpressing mice (Combi-Slug) exhibit an increase in the WAT size. Consistent with in vivo data, Slug-deficient mouse embryonic fibroblasts (MEFs) showed a dramatically reduced capacity for adipogenesis in vitro and there was extensive lipid accumulation in Combi-Slug MEFs. The analysis of adipogenic gene expression both in vivo and in vitro showed that peroxisome proliferator-activated factor gamma 2 (PPAR gamma 2) expression was altered. Complementation studies rescued this phenotype, indicating that WAT alterations induced by Slug are reversible. Our results further show a differential histone deacetylase recruitment to the PPAR gamma 2 promoter in a tissue- and Slug-dependent manner. Our results connect, for the first time, adipogenesis with the requirement of a critical level of an EMT regulator in mammals. This work may lead to the development of targeted drugs for the treatment of patients with obesity and/or lipodystrophy.