Lipid signalling in disease.
Signalling lipids such as eicosanoids, phosphoinositides, sphingolipids and fatty acids control important cellular processes, including cell proliferation, apoptosis, metabolism and migration. Extracellular signals from cytokines, growth factors and nutrients control the activity of a key set of lipid-modifying enzymes: phospholipases, prostaglandin synthase, 5-lipoxygenase, phosphoinositide 3-kinase, sphingosine kinase and sphingomyelinase. These enzymes and their downstream targets constitute a complex lipid signalling network with multiple nodes of interaction and cross-regulation. Imbalances in this network contribute to the pathogenesis of human disease. Although the function of a particular signalling lipid is traditionally studied in isolation, this review attempts a more integrated overview of the key role of these signalling lipids in inflammation, cancer and metabolic disease, and discusses emerging strategies for therapeutic intervention.
Wymann
Matthias P
MP
Institute of Biochemistry and Genetics, Department of Biomedicine, University of Basel, Mattenstrasse 28, CH-4058 Basel, Switzerland. matthias.wymann@unibas.ch
Schneiter
Roger
R
D000818:Animals; D002384:Catalysis; D002467:Cell Nucleus / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*; D008246:Lysophospholipids / Q000378:metabolism; D008954:Models, Biological; D010766:Phosphorylation; D015398:Signal Transduction; D013109:Sphingomyelins / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism
D016207:Cytokines; D007328:Insulin; D008055:Lipids; D008246:Lysophospholipids; D013109:Sphingomyelins; C060506:sphingosine 1-phosphate; D013110:Sphingosine