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DOI | 10.1126/science.aav3722 |
Targeting a ceramide double bond improves insulin resistance and hepatic steatosis | |
Chaurasia, Bhagirath1,2; Tippetts, Trevor S.1,2; Monibas, Rafael Mayoral3; Liu, Jinqi3,10; Li, Ying1,2; Wang, Liping1,2; Wilkerson, Joseph L.1,2; Sweeney, C. Rufus1,2; Pereira, Renato Felipe4; Sumida, Doris Hissako4; Maschek, J. Alan2,5; Cox, James E.2,5; Kaddai, Vincent1,2; Lancaster, Graeme Iain6; Siddique, Monowarul Mobin7; Poss, Annelise1,2; Pearson, Mackenzie8; Satapati, Santhosh3; Zhou, Heather3; McLaren, David G.3; Previs, Stephen F.3; Chen, Ying3; Qian, Ying3; Petrov, Aleksandr3; Wu, Margaret3; Shen, Xiaolan3; Yao, Jun3; Nunes, Christian N.3; Howard, Andrew D.3; Wang, Liangsu3,11; Erion, Mark D.3,12; Rutter, Jared2,5,9; Holland, William L.1,2; Kelley, David E.3; Summers, Scott A.1,2 | |
2019-07-26 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 365期号:6451页码:386-+ |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Brazil; Australia; Brunei |
英文摘要 | 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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000477703100042 |
WOS关键词 | FATTY-ACID UPTAKE ; PKC-ZETA ; INHIBITION ; METABOLISM ; TRANSPORT ; GLUCOSE ; PROTEIN ; AKT ; DIHYDROCERAMIDES ; SPHINGOLIPIDS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201950 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Univ Utah, Dept Nutr & Integrat Physiol, Salt Lake City, UT 84112 USA; 2.Univ Utah, Diabet & Metab Res Ctr, Salt Lake City, UT 84112 USA; 3.Merck, Merck Res Labs, Kenilworth, NJ 07033 USA; 4.Sao Paulo State Univ UNESP, Sch Dent, BR-16015 Aracatuba, Brazil; 5.Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA; 6.Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia; 7.Univ Brunei Darussalam, Fac Sci, Gadong 1410, Brunei; 8.SCIEX Ltd, Framingham, MA 01701 USA; 9.Howard Hughes Med Inst, Salt Lake City, UT 84112 USA; 10.Bristol Myers Squibb, Princeton, NJ 08648 USA; 11.Morph Therapeut, Waltham, MA 02451 USA; 12.Johnson & Johnson, Spring House, PA 19477 USA |
推荐引用方式 GB/T 7714 | Chaurasia, Bhagirath,Tippetts, Trevor S.,Monibas, Rafael Mayoral,et al. Targeting a ceramide double bond improves insulin resistance and hepatic steatosis[J]. SCIENCE,2019,365(6451):386-+. |
APA | Chaurasia, Bhagirath.,Tippetts, Trevor S..,Monibas, Rafael Mayoral.,Liu, Jinqi.,Li, Ying.,...&Summers, Scott A..(2019).Targeting a ceramide double bond improves insulin resistance and hepatic steatosis.SCIENCE,365(6451),386-+. |
MLA | Chaurasia, Bhagirath,et al."Targeting a ceramide double bond improves insulin resistance and hepatic steatosis".SCIENCE 365.6451(2019):386-+. |
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