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Orphan Nuclear Receptors and the Regulation of Nutrient Metabolism: Understanding Obesity

机译:孤儿核受体和营养代谢的调节:了解肥胖。

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摘要

Nuclear hormone receptors (NRs) are a superfamily of eukaryotic ligand-depen-dent transcription factors that translate endocrine, metabolic, nutritional, developmental, and pathophysiological signals into gene regulation. Members of the NR superfamily(on the basis of sequence homology) that lack identified natural and/or synthetic ligands are/were classified as "orphan" NRs. These members of the NR superfamily are abundantly expressed in tissues associated with major metabolic activity, such as skeletal muscle, adipose, and liver. Subsequently, in vivo genetic studies on these orphan NRs and exploitation of novel natural and synthetic agonists has revealed that orphan NRs regulate 1) carbohydrate, lipid, and energy homeostasis in a tissue-specificmanner, and 2) the pathophysiology of dyslipidemia, obesity, Type 2 diabetes, and cardiovascular disease. This review discusses key studies that have implicated the orphan NRs as organ-specific regulators of metabolism and mediators of adverse pathophysiological effects. The emerging discovery of novel endogenous orphan NR ligands and synthetic agonists has provided the foundation for therapeutic exploitation of the orphans in the treatment of metabolic disease.
机译:核激素受体(NRs)是真核配体依赖性转录因子的超家族,可将内分泌,代谢,营养,发育和病理生理信号转化为基因调控。缺乏已鉴定的天然和/或合成配体的NR超家族成员(基于序列同源性)被归类为“孤儿” NR。 NR超家族的这些成员在与主要代谢活动相关的组织中大量表达,例如骨骼肌,脂肪和肝脏。随后,对这些孤儿NRs的体内遗传研究以及对新型天然和合成激动剂的开发表明,孤儿NRs以组织特异性方式调节1)碳水化合物,脂质和能量稳态,以及2)血脂异常,肥胖症,类型的病理生理学2糖尿病和心血管疾病。这篇评论讨论了关键研究,这些研究牵涉到孤儿NRs作为代谢的器官特异性调节剂和不良病理生理作用的介质。新型内源性孤儿NR配体和合成激动剂的新发现为治疗代谢疾病中的孤儿提供了治疗基础。

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