title: Sphingolipids and glycerophospholipids - The "ying and yang" of lipotoxicity in metabolic diseases.
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.
authors.affiliation: Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge. Cambridge, UK. Electronic address: sr441@medschl.cam.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Rodriguez-Cuenca
authors.affiliation: Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge. Cambridge, UK.
authors.forename: V
authors.initials: V
authors.lastname: Pellegrinelli
authors.affiliation: Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge. Cambridge, UK.
authors.forename: M
authors.initials: M
authors.lastname: Campbell
authors.affiliation: Turku Centre for Biotechnology, University of Turku and Åbo Akademi University, FI -20520 Turku, Finland.
authors.forename: M
authors.initials: M
authors.lastname: Oresic
authors.affiliation: Metabolic Research Laboratories, Wellcome Trust MRC Institute of Metabolic Science, Addenbrooke's Hospital, University of Cambridge. Cambridge, UK; Wellcome Trust Sanger Institute, Hinxton, UK. Electronic address: ajv22@medschl.cam.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Vidal-Puig
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D020404:Glycerophospholipids / Q000378:metabolism*; D006801:Humans; D008659:Metabolic Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D020404:Glycerophospholipids; D013107:Sphingolipids
keywords: Glycerophospholipids; Lipotoxicity; Sphingolipids