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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Targeting a ceramide double bond improves insulin resistance and hepatic steatosis

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Author(s):
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Chaurasia, Bhagirath [1, 2] ; Tippetts, Trevor S. [1, 2] ; Monibas, Rafael Mayoral [3] ; Liu, Jinqi [3, 4] ; Li, Ying [1, 2] ; Wang, Liping [1, 2] ; Wilkerson, Joseph L. [1, 2] ; Sweeney, C. Rufus [1, 2] ; Pereira, Renato Felipe [5] ; Sumida, Doris Hissako [5] ; Maschek, J. Alan [2, 6] ; Cox, James E. [2, 6] ; Kaddai, Vincent [1, 2] ; Lancaster, Graeme Iain [7] ; Siddique, Monowarul Mobin [8] ; Poss, Annelise [1, 2] ; Pearson, Mackenzie [9] ; Satapati, Santhosh [3] ; Zhou, Heather [3] ; McLaren, David G. [3] ; Previs, Stephen F. [3] ; Chen, Ying [3] ; Qian, Ying [3] ; Petrov, Aleksandr [3] ; Wu, Margaret [3] ; Shen, Xiaolan [3] ; Yao, Jun [3] ; Nunes, Christian N. [3] ; Howard, Andrew D. [3] ; Wang, Liangsu [3, 10] ; Erion, Mark D. [3, 11] ; Rutter, Jared [2, 6, 12] ; Holland, William L. [1, 2] ; Kelley, David E. [3] ; Summers, Scott A. [1, 2]
Total Authors: 35
Affiliation:
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[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] Bristol Myers Squibb, Princeton, NJ 08648 - USA
[5] Sao Paulo State Univ UNESP, Sch Dent, BR-16015 Aracatuba - Brazil
[6] Univ Utah, Dept Biochem, Salt Lake City, UT 84112 - USA
[7] Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004 - Australia
[8] Univ Brunei Darussalam, Fac Sci, Gadong 1410 - Brunei
[9] SCIEX Ltd, Framingham, MA 01701 - USA
[10] Morph Therapeut, Waltham, MA 02451 - USA
[11] Johnson & Johnson, Spring House, PA 19477 - USA
[12] Howard Hughes Med Inst, Salt Lake City, UT 84112 - USA
Total Affiliations: 12
Document type: Journal article
Source: Science; v. 365, n. 6451, p. 386+, JUL 26 2019.
Web of Science Citations: 40
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. (AU)

FAPESP's process: 14/17619-6 - STUDY ABOUT THE MECHANISMS INVOLVED IN THE DEVELOPMENT OF INSULIN RESISTANCE IN RATS WITH PERIAPICAL LESION
Grantee:Renato Felipe Pereira
Support type: Scholarships in Brazil - Doctorate