Glucocorticoid Receptor and Adipocyte Biology.
Glucocorticoid Receptor and Adipocyte Biology.
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DOI：
10.32527/2018/101373
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发表时间：
2018-01-01
影响因子：
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通讯作者：
Wang, Jen-Chywan
中科院分区：
文献类型：
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作者：
Lee, Rebecca A;Harris, Charles A;Wang, Jen-Chywan
糖皮质激素是类固醇激素，在压力（例如禁食和饥饿）期间的代谢适应中发挥关键作用，以维持血糖水平。然而，过量和长期接触糖皮质激素会导致代谢综合征，包括胰岛素抵抗、血脂异常和高血糖。对代谢紊乱动物模型的研究经常表明，抑制糖皮质激素信号传导可以改善胰岛素敏感性和代谢特征。糖皮质激素通过细胞内糖皮质激素受体 (GR) 传递信号，该受体是一种转录调节因子。脂肪细胞是一种在 GR 的影响下有助于全身代谢稳态的细胞类型。糖皮质激素对脂肪组织的作用很复杂。根据不同的生理或病理生理状态以及不同的脂肪库，糖皮质激素可以增加或减少脂肪组织中的脂质储存。在啮齿动物中，糖皮质激素已被证明可以降低棕色脂肪细胞的产热活性。然而，在人类急性糖皮质激素暴露中，糖皮质激素起到促进生热作用。在本文中，我们将回顾最近关于脂肪细胞中GR复杂代谢功能机制的研究。这些包括对脂肪细胞特异性 GR 敲除小鼠的代谢结果的研究，以及介导脂肪细胞中糖皮质激素作用的新型 GR 主要靶基因的鉴定。
Glucocorticoids are steroid hormones that play a key role in metabolic adaptations during stress, such as fasting and starvation, in order to maintain plasma glucose levels. Excess and chronic glucocorticoid exposure, however, causes metabolic syndrome including insulin resistance, dyslipidemia, and hyperglycemia. Studies in animal models of metabolic disorders frequently demonstrate that suppressing glucocorticoid signaling improves insulin sensitivity and metabolic profiles. Glucocorticoids convey their signals through an intracellular glucocorticoid receptor (GR), which is a transcriptional regulator. The adipocyte is one cell type that contributes to whole body metabolic homeostasis under the influence of GR. Glucocorticoids' functions on adipose tissues are complex. Depending on various physiological or pathophysiological states as well as distinct fat depots, glucocorticoids can either increase or decrease lipid storage in adipose tissues. In rodents, glucocorticoids have been shown to reduce the thermogenic activity of brown adipocytes. However, in human acute glucocorticoid exposure, glucocorticoids act to promote thermogenesis. In this article, we will review the recent studies on the mechanisms underlying the complex metabolic functions of GR in adipocytes. These include studies of the metabolic outcomes of adipocyte specific GR knockout mice and identification of novel GR primary target genes that mediate glucocorticoid action in adipocytes.