Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8358845 | Progress in Lipid Research | 2017 | 16 Pages |
Abstract
Sphingolipids in general and ceramides in particular, contribute to pathophysiological mechanisms by modifying signalling and metabolic pathways. Here, we present the available evidence for a bidirectional homeostatic crosstalk between sphingolipids and glycerophospholipids, whose dysregulation contributes to lipotoxicity induced metabolic stress. The initial evidence for this crosstalk originates from simulated models designed to investigate the biophysical properties of sphingolipids in plasma membrane representations. In this review, we reinterpret some of the original findings and conceptualise them as a sort of “ying/yang” interaction model of opposed/complementary forces, which is consistent with the current knowledge of lipid homeostasis and pathophysiology. We also propose that the dysregulation of the balance between sphingolipids and glycerophospholipids results in a lipotoxic insult relevant in the pathophysiology of common metabolic diseases, typically characterised by their increased ceramide/sphingosine pools.
Keywords
PI3KCERKC1PCCTαSREBP1SphK1CerSCERTPLA2SRESMaseS1PPLCPLDHDLRAC-alpha serine/threonine-protein kinasephospholipase A2AktsphingolipidssphingomyelinSphingosine kinase 1Sphingosine-1-phosphatesphingomyelin synthasesphingomyelinaseArachidonic acidtriglyceridePleckstrin homology domainCeramide kinaseCeramide-1-phosphateLipotoxicityceramide synthasePlatelet activating factorsterol regulatory elementphosphatidylinositolphosphatidylcholinephosphatidylethanolaminePhosphatidylserinePhosphatidylinositol 3-kinasephospholipase CPhospholipase DHigh-density lipoproteinsPAFsterol regulatory element-binding protein 1ceramide transport proteinSerine palmitoyltransferaseSMSglycerophospholipids
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Authors
S. Rodriguez-Cuenca, V. Pellegrinelli, M. Campbell, M. Oresic, A. Vidal-Puig,