GSTDTAP  > 地球科学
DOI10.1126/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
ISSN0036-8075
EISSN1095-9203
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
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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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