Journal
PROGRESS IN LIPID RESEARCH
Volume 66, Issue -, Pages 14-29Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.plipres.2017.01.002
Keywords
Sphingolipids; Glycerophospholipids; Lipotoxicity
Funding
- Medical Research Council [MC_UU_12012/2]
- Biotechnology and Biological Sciences Research Council [BB/H002731/1] Funding Source: researchfish
- British Heart Foundation [RG/12/13/29853] Funding Source: researchfish
- Medical Research Council [G0400192, MC_UU_12012/5/B, MC_UU_12012/2] Funding Source: researchfish
- BBSRC [BB/H002731/1] Funding Source: UKRI
- MRC [MC_UU_12012/2, G0400192] Funding Source: UKRI
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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. (C) 2017 Published by Elsevier Ltd.
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