Ceramide and sphingosine 1-phosphate in adipose dysfunction. (April 2019)

• Record Type: Journal Article
• Authors: Fang, Zijian; Pyne, Susan; Pyne, Nigel J.
• Is Part Of: Progress in lipid research. Volume 74(2019)
• Page Start: 145
• Page End: 159
• Publication Date: 2019-04
• Subjects: ADRB3 β3-adrenergic receptor -- AKT protein kinase B -- AMSC adipose tissue-derived mesenchymal stem cell -- ApoM apolipoprotein M -- AP1 activator protein 1 -- aSMase acid sphingomyelinase -- αSMA α-smooth muscle actin -- ATGL adipose triglyceride lipase -- ATM adipose tissue macrophages -- BMI body mass index -- BMP bone morphogenetic protein -- CCL5 chemokine ligand 5 -- C/EBPs CCAAT/enhancer-binding proteins -- CEM caveolin-enriched micro-domains -- CerS ceramide synthase -- CL CL-316243 (β3-adrenergic agonist) -- DAG diacylglycerol -- Degs1 dihydroceramide desaturase -- DIO diet-induced obesity -- DMS dimethylsphingosine -- DHS dihydrosphingosine -- EGF epidermal growth factor -- ER endoplasmic reticulum -- ERK1/2 extracellular signal-regulated kinase 1 and 2 -- FABP4 fatty acid-binding protein 4 -- FOXO forkhead box protein O -- FTY720 fingolimod (2-Amino-2-[2-(4-octyl-phenyl)-ethyl]-propane-1, 3-diol) -- GLUT4 glucose transporter 4 -- GSK3β glycogen synthase kinase 3 beta -- GWAS genome-wide association study -- HDAC1/2 histone deacetylase 1 and 2 -- HDL high density lipoprotein -- HFD high fat diet -- HSL hormone-sensitive lipase -- IFNγ interferon gamma -- IL-1β interleukin-1β -- IKK-β inhibitor of nuclear factor kappa-B kinase subunit beta -- IR insulin receptor -- IRS insulin receptor substrate -- JAK Janus kinases -- c-JNK c-Jun N-terminal kinase -- JTE-013 S1P2 antagonist -- KC keratinocyte-derived chemokine -- LDL low density lipoprotein -- LPP lipid phosphate phosphatase -- LPS lipopolysaccharides -- MAGL monoglyceride lipase -- MAPK mitogen-activated protein kinase -- MCP-1 monocyte chemoattractant protein 1 -- mTOR mammalian target of rapamycin -- NEFA Non esterified fatty acid -- NF-κB nuclear factor kappa-light-chain-enhancer of activated B cells -- NLRP3 NACHT LRR and PYD domains-containing protein 3 -- nSMase neutral sphingomyelinase -- PCNA proliferating cell nuclear antigen -- PDE3B phosphodiesterase 3B -- PDK phosphoinositide-dependent kinases -- PHB2 prohibitin 2 -- PMA phorbol 12-myristate 13-acetate -- PI3K phosphoinositide 3-kinase -- PIP3 phosphatidylinositol (3, 4, 5)-trisphosphate -- PKA protein kinase A -- PKC protein kinase C -- PKD protein kinase D -- PLC phospholipase C -- PPARγ peroxisome proliferator-activated receptor gamma -- PP2A protein phosphatase-2A -- PTEN phosphatase and tensin homologue -- PTP1B protein-tyrosine phosphatase 1B -- S1P sphingosine 1-phosphate -- S1P1-5 S1P receptor 1-5 -- S6K ribosomal protein S6 kinase -- SPHK I or SKI-II (2-(p-Hydroxyanilino)-4-(p-chlorophenyl) thiazole) -- Smpd1 acid sphingomyelinase gene -- SphK sphingosine kinase -- SOCS3 Suppressor of cytokine signaling 3 -- SPT serine palmitoyl transferase -- SREBF1 sterol regulatory element-binding transcription factor 1 -- STAT3 signal transducer and activator of transcription 3 -- T2D type 2 diabetes -- TGFβ transforming growth factor beta -- TLR Toll-like receptors -- TNFα tumor necrosis factor alpha -- TRAF2 TNF receptor-associated factor 2 -- UCP-1 uncoupling protein-1 -- VEGF vascular endothelial growth factor -- VLDL very low density lipoprotein -- VPC23019 S1P1/3 antagonist -- ZLC Zucker lean normoglycemic control -- 5c 2, 2-dimethyl-4S-(1-oxo-2-hexadecyn-1-yl)-1, 1-dimethylethylester-3-oxazolidine-carboxylic acid.; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipiden; 572.57
• DOI: 10.1016/j.plipres.2019.04.001
• Languages: English
• ISSNs: 0163-7827

Abstract

Abstract: The increased adipose tissue mass of obese individuals enhances the risk of metabolic syndrome, type 2 diabetes and cardiovascular diseases. During pathological expansion of adipose tissue, multiple molecular controls of lipid storage, adipocyte turn-over and endocrine secretion are perturbed and abnormal lipid metabolism results in a distinct lipid profile. There is a role for ceramides and sphingosine 1-phosphate (S1P) in inducing adipose dysfunction. For instance, the alteration of ceramide biosynthesis, through the de-regulation of key enzymes, results in aberrant formation of ceramides (e.g. C16:0 and C18:0 ) which block insulin signaling and promote adipose inflammation. Furthermore, S1P can induce defective adipose tissue phenotypes by promoting chronic inflammation and inhibiting adipogenesis. These abnormal changes are discussed in the context of possible therapeutic approaches to re-establish normal adipose function and to, thereby, increase insulin sensitivity in type 2 diabetes. Such novel approaches include blockade of ceramide biosynthesis using inhibitors of sphingomyelinase or dihydroceramide desaturase and by antagonism of S1P receptors, such as S1P2 .