Dihydroceramide desaturase 1, the gatekeeper of ceramide induced lipotoxicity

被引:64
作者
Rodriguez-Cuenca, S. [1 ]
Barbarroja, N. [2 ]
Vidal-Puig, A. [1 ,3 ]
机构
[1] Univ Cambridge, Addenbrookes Hosp, Wellcome Trust MRC Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England
[2] Reina Sofia Univ Hosp, IMIBIC, Cordoba, Spain
[3] Wellcome Trust Sanger Inst, Hinxton, England
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2015年 / 1851卷 / 01期
基金
英国医学研究理事会;
关键词
Dihydroceramide; Lipotoxicity; DEGS1; Desaturase; DIET-INDUCED OBESITY; LECITHIN RETINOL ACYLTRANSFERASE; PORPHYROMONAS-GINGIVALIS LIPIDS; INDUCED INSULIN-RESISTANCE; DE-NOVO SYNTHESIS; VITAMIN-A; GENE-EXPRESSION; INDUCED APOPTOSIS; SPHINGOLIPID METABOLISM; BIOLOGICAL-ACTIVITY;
D O I
10.1016/j.bbalip.2014.09.021
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The pathogenic relevance of sphingolipid metabolism is increasingly being recognised. Here we elaborate on a new player within the sphingolipid field: the degs1 enzyme, a recently discovered enzyme that catalyses the final step in the de novo biosynthesis of ceramides controlling the step from dihydroceramides to ceramides. Here, we describe its function and dysregulation by factors such as oxidative stress, hypoxia and inflammation and provide evidence indicating that dihydroceramides constitute a biologically active molecule from the sphingolipid family with certain differential characteristics with respect to its delta-4 unsaturated counterparts, the ceramides. Finally we present pathophysiological scenarios characterised by specific increases in dihydroceramide that challenge the concept that "all ceramides species are the same". This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:40 / 50
页数:11
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