Notch信号通路作为一种新型的代谢调节因子。
Notch signaling as a novel regulator of metabolism.
作者信息
Bi Pengpeng, Kuang Shihuan
机构信息
Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA.
Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA; Center for Cancer Research, Purdue University, West Lafayette, IN 47907, USA.
出版信息
Trends Endocrinol Metab. 2015 May;26(5):248-55. doi: 10.1016/j.tem.2015.02.006. Epub 2015 Mar 21.
Abstract
Evolutionarily unprepared for modern high-calorie diets and sedentary lifestyles, humans are now unprecedentedly susceptible to metabolic disorders such as obesity, type 2 diabetes (T2D), nonalcoholic fatty liver, and cardiovascular disease. These metabolic conditions are intertwined, together known as metabolic syndrome, and compromise human life quality as well as lives. Notch signaling, a fundamental signal transduction pathway critical for cell-cell communication and development, has recently been recognized as a key player in metabolism. This review summarizes the emerging roles of Notch signaling in regulating the metabolism of various cell and tissue types, with emphasis on the underlying molecular mechanisms and the potential of targeting this signal axis to treat metabolic diseases.
摘要
由于进化上未对现代高热量饮食和久坐不动的生活方式做好准备，人类现在极易患上肥胖症、2型糖尿病（T2D）、非酒精性脂肪肝和心血管疾病等代谢紊乱疾病。这些代谢状况相互交织，统称为代谢综合征，会损害人类的生活质量乃至生命。Notch信号通路是一种对细胞间通讯和发育至关重要的基本信号转导途径，最近被认为是代谢中的关键参与者。本综述总结了Notch信号通路在调节各种细胞和组织类型代谢方面的新作用，重点介绍了潜在的分子机制以及靶向该信号轴治疗代谢疾病的潜力。
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2
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3
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Nat Rev Endocrinol. 2014 Nov;10(11):642-4. doi: 10.1038/nrendo.2014.141. Epub 2014 Aug 12.
4
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