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Monowarul Mobin Siddique

时间:2019-08-01 06:45 来源:www.haosftl.com 作者:好私服

靶向神经酰胺双键可以改善胰岛素抗药性和脂肪肝,这一成果由犹他大学Scott A. Summers研究组取得。相关论文于2019年7月26日发表于国际顶尖学术期刊《科学》杂志上。

通过基因工程小鼠,该课题组人员删除二氢神经酰胺去饱和酶1 (DES1),该酶能够将保守性双键插入到神经酰胺和其他主要的鞘脂类的骨架内。从整个动物中消融DES1,或在肝脏组织或脂肪组织中特异性删除,能够解决小鼠内由瘦蛋白缺乏和肥胖饮食引发的脂肪肝和胰岛素抗药性。机制研究揭示神经酰胺的作用能促进脂质吸收和存储,削弱葡萄糖利用。当(二氢)神经酰胺缺乏关键的双键时,上述功能无法重现。这些研究表明抑制DES1可能提供治疗脂肪肝和代谢紊乱的方法。

研究人员表示,神经酰胺会产生脂毒性,进而导致糖尿病,脂肪肝和心脏疾病。

附:英文原文

Title: Targeting a ceramide double bond improves insulin resistance and hepatic steatosis

Author: Bhagirath Chaurasia, Trevor S. Tippetts, Rafael Mayoral Monibas, Jinqi Liu, Ying Li, Liping Wang, Joseph L. Wilkerson, C. Rufus Sweeney, Renato Felipe Pereira, Doris Hissako Sumida, J. Alan Maschek, James E. Cox, Vincent Kaddai, Graeme Iain Lancaster, Monowarul Mobin Siddique, Annelise Poss, Mackenzie Pearson, Santhosh Satapati, Heather Zhou, David G. McLaren, Stephen F. Previs, Ying Chen, Ying Qian, Aleksandr Petrov, Margaret Wu, Xiaolan Shen, Jun Yao, Christian N. Nunes, Andrew D. Howard, Liangsu Wang, Mark D. Erion, Jared Rutter, William L. Holland, David E. Kelley, Scott A. Summers

Issue&Volume:Vol 365 Issue 6451

Abstract: Ceramides contribute to the lipotoxicity that underlies diabetes, hepatic steatosis, and heart disease. By genetically engineering mice, we deleted the enzyme dihydroceramide desaturase 1 (DES1), which normally inserts a conserved double bond into the backbone of ceramides and other predominant sphingolipids. Ablation of DES1 from whole animals or tissue-specific deletion in the liver and/or adipose tissue resolved hepatic steatosis and insulin resistance in mice caused by leptin deficiency or obesogenic diets. Mechanistic studies revealed ceramide actions that promoted lipid uptake and storage and impaired glucose utilization, none of which could be recapitulated by (dihydro)ceramides that lacked the critical double bond. These studies suggest that inhibition of DES1 may provide a means of treating hepatic steatosis and metabolic disorders.

DOI: 10.1126/science.aav3722

Source:https://science.sciencemag.org/content/365/6451/386

期刊信息

Science:《科学》,创刊于1880年。隶属于美国科学促进会,最新IF:41.037

官方网址:https://www.sciencemag.org/

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本期文章:《科学》:Vol 365 Issue 6451

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