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Regulation of NR4A by nutritional status gender postnatal development and hormonal deficiency

机译:通过营养状况性别产后发育和激素缺乏对NR4A的调节

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摘要

The NR4A is a subfamily of the orphan nuclear receptors (NR) superfamily constituted by three well characterized members: Nur77 (NR4A1), Nurr1 (NR4A2) and Nor 1 (NR4A3). They are implicated in numerous biological processes as DNA repair, arteriosclerosis, cell apoptosis, carcinogenesis and metabolism. Several studies have demonstrated the role of this subfamily on glucose metabolism, insulin sensitivity and energy balance. These studies have focused mainly in liver and skeletal muscle. However, its potential role in white adipose tissue (WAT), one of the most important tissues involved in the regulation of energy homeostasis, is not well-studied. The aim of this work was to elucidate the regulation of NR4A in WAT under different physiological and pathophysiological settings involved in energy balance such as fasting, postnatal development, gender, hormonal deficiency and pregnancy. We compared NR4A mRNA expression of Nur77, Nurr1 and Nor 1 and found a clear regulation by nutritional status, since the expression of the 3 isoforms is increased after fasting in a leptin-independent manner and sex steroid hormones also modulate NR4A expression in males and females. Our findings indicate that NR4A are regulated by different physiological and pathophysiological settings known to be associated with marked alterations in glucose metabolism and energy status.
机译:NR4A是孤儿核受体(NR)超家族的一个亚家族,由三个特征明确的成员组成:Nur77(NR4A1),Nurr1(NR4A2)和Nor 1(NR4A3)。它们与DNA修复,动脉硬化,细胞凋亡,致癌作用和代谢等众多生物学过程有关。几项研究证明了该亚家族对葡萄糖代谢,胰岛素敏感性和能量平衡的作用。这些研究主要集中在肝脏和骨骼肌。然而,其在白色脂肪组织(WAT)中的潜在作用尚不清楚,WAT是能量稳态调节中最重要的组织之一。这项工作的目的是阐明在能量平衡(如禁食,产后发育,性别,荷尔蒙缺乏和怀孕)所涉及的不同生理和病理生理环境下,WAT中NR4A的调控。我们比较了Nur77,Nurr1和Nor 1的NR4A mRNA表达,并发现了营养状况的明确调控,因为3种亚型的表达以禁食瘦素的方式增加了,而性类固醇激素也调节了男性和女性的NR4A表达。 。我们的发现表明,NR4A受已知与葡萄糖代谢和能量状态显着改变有关的不同生理和病理生理环境的调节。

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