CGI-58/ABHD5 is a coenzyme A-dependent lysophosphatidic acid acyltransferase

Abstract

Mutations in human CGI-58/ABHD5 cause Chanarin-Dorfman syndrome (CDS), characterized by excessive storage of triacylglycerol in tissues. CGI-58 is an α/β-hydrolase fold enzyme expressed in all vertebrates. The carboxyl terminus includes a highly conserved consensus sequence (HXXXXD) for acyltransferase activity. Mouse CGI-58 was expressed in Escherichia coli as a fusion protein with two amino terminal 6-histidine tags. Recombinant CGI-58 displayed acyl-CoA-dependent acyltransferase activity to lysophosphatidic acid, but not to other lysophospholipid or neutral glycerolipid acceptors. Production of phosphatidic acid increased with time and increasing concentrations of recombinant CGI-58 and was optimal between pH 7.0 and 8.5. The enzyme showed saturation kinetics with respect to 1-oleoyl-lysophosphatidic acid and oleoyl-CoA and preference for arachidonoyl-CoA and oleoyl-CoA. The enzyme showed slight preference for 1-oleoyl lysophosphatidic acid over 1-palmitoyl, 1-stearoyl, or 1-arachidonoyl lysophosphatidic acid. Recombinant CGI-58 showed intrinsic fluorescence for tryptophan that was quenched by the addition of 1-oleoyl-lysophosphatidic acid, oleoyl-CoA, arachidonoyl-CoA, and palmitoyl-CoA, but not by lysophosphatidyl choline. Expression of CGI-58 in fibroblasts from humans with CDS increased the incorporation of radiolabeled fatty acids released from the lipolysis of stored triacylglycerols into phospholipids. CGI-58 is a CoA-dependent lysophosphatidic acid acyltransferase that channels fatty acids released from the hydrolysis of stored triacylglycerols into phospholipids. Mutations in human CGI-58/ABHD5 cause Chanarin-Dorfman syndrome (CDS), characterized by excessive storage of triacylglycerol in tissues. CGI-58 is an α/β-hydrolase fold enzyme expressed in all vertebrates. The carboxyl terminus includes a highly conserved consensus sequence (HXXXXD) for acyltransferase activity. Mouse CGI-58 was expressed in Escherichia coli as a fusion protein with two amino terminal 6-histidine tags. Recombinant CGI-58 displayed acyl-CoA-dependent acyltransferase activity to lysophosphatidic acid, but not to other lysophospholipid or neutral glycerolipid acceptors. Production of phosphatidic acid increased with time and increasing concentrations of recombinant CGI-58 and was optimal between pH 7.0 and 8.5. The enzyme showed saturation kinetics with respect to 1-oleoyl-lysophosphatidic acid and oleoyl-CoA and preference for arachidonoyl-CoA and oleoyl-CoA. The enzyme showed slight preference for 1-oleoyl lysophosphatidic acid over 1-palmitoyl, 1-stearoyl, or 1-arachidonoyl lysophosphatidic acid. Recombinant CGI-58 showed intrinsic fluorescence for tryptophan that was quenched by the addition of 1-oleoyl-lysophosphatidic acid, oleoyl-CoA, arachidonoyl-CoA, and palmitoyl-CoA, but not by lysophosphatidyl choline. Expression of CGI-58 in fibroblasts from humans with CDS increased the incorporation of radiolabeled fatty acids released from the lipolysis of stored triacylglycerols into phospholipids. CGI-58 is a CoA-dependent lysophosphatidic acid acyltransferase that channels fatty acids released from the hydrolysis of stored triacylglycerols into phospholipids. Most cells of vertebrates have the capacity to store triacylglycerols in cytoplasmic lipid droplets. The hydrolysis of these lipids provides a source of substrates for the synthesis of phospholipids used for membrane repair and expansion, and metabolism to fuel ATP production. In adipocytes, the binding of catecholamines to β-adrenergic receptors at the cell surface triggers a signaling cascade that ultimately activates lipolysis through a complex mechanism requiring the protein kinase A-mediated phosphorylation of multiple proteins, including a major cytosolic lipase named hormone-sensitive lipase and the structural lipid droplet protein perilipin A (1Brasaemle D.L. Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis.J. Lipid Res. 2007; 48: 2547-2559Abstract Full Text Full Text PDF PubMed Scopus (768) Google Scholar). Additional components of the lipolytic pathway include adipose triglyceride lipase (ATGL, also known as desnutrin), monoglyceride lipase, and CGI-58/ABHD5 (comparative genome identification 58/α/β hydrolase domain 5). Details of how these various components work together are still poorly understood and the subject of active investigation. Even less is known about how lipolysis of stored neutral lipids is catalyzed and controlled in other nonadipose cells. CGI-58 plays an important role in the maintenance of triacylglycerol homeostasis in many types of cells. Mutations in the gene for CGI-58 cause a neutral lipid storage disorder in humans called Chanarin-Dorfman syndrome (CDS) (2Lefevre C. Jobard F. Caux F. Bouadjar B. Karaduman A. Heilig R. Lakhdar H. Wollenberg A. Verret J.L. Weissenbach J. et al.Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome.Am. J. Hum. Genet. 2001; 69: 1002-1012Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar). CDS is characterized by ichthyosis, hepatosteatosis, and hepatomegaly, developmental defects, and the excessive accumulation of triacylglycerols in lipid droplets in many types of cells, including basal keratinocytes, hepatocytes, myocytes, and leukocytes (2Lefevre C. Jobard F. Caux F. Bouadjar B. Karaduman A. Heilig R. Lakhdar H. Wollenberg A. Verret J.L. Weissenbach J. et al.Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome.Am. J. Hum. Genet. 2001; 69: 1002-1012Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar, 3Igal R.A. Rhoads J.M. Coleman R.A. Neutral lipid storage disease with fatty liver and cholestasis.J. Pediatr. Gastroenterol. Nutr. 1997; 25: 541-547Crossref PubMed Scopus (63) Google Scholar, 4Srebrnik A. Brenner S. Ilie B. Messer G. Dorfman-Chanarin syndrome: morphologic studies and presentation of new cases.Am. J. Dermatopathol. 1998; 20: 79-85Crossref PubMed Scopus (34) Google Scholar, 5Wollenberg A. Geiger E. Schaller M. Wolff H. Dorfman-Chanarin syndrome in a Turkish kindred: conductor diagnosis requires analysis of multiple eosinophils.Acta Derm. Venereol. 2000; 80: 39-43Crossref PubMed Scopus (28) Google Scholar). CGI-58 is a member of the lipase subfamily of α/β-hydrolase fold enzymes (2Lefevre C. Jobard F. Caux F. Bouadjar B. Karaduman A. Heilig R. Lakhdar H. Wollenberg A. Verret J.L. Weissenbach J. et al.Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome.Am. J. Hum. Genet. 2001; 69: 1002-1012Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar). Unlike lipases, CGI-58 lacks a complete catalytic triad; an asparagine residue replaces the usual nucleophilic serine residue within a conserved consensus sequence of GXSXG (where X represents any amino acid). Consistent with this substitution, recombinant CGI-58 shows no lipase activity (6Lass A. Zimmermann R. Haemmerle G. Riederer M. Schoiswohl G. Schweiger M. Kienesberger P. Strauss J.G. Gorkiewicz G. Zechner R. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome.Cell Metab. 2006; 3: 309-319Abstract Full Text Full Text PDF PubMed Scopus (681) Google Scholar). Nonetheless, experiments conducted in vitro have shown that the addition of CGI-58 significantly increases triacylglycerol hydrolase activity of cell lysates containing the lipase ATGL (6Lass A. Zimmermann R. Haemmerle G. Riederer M. Schoiswohl G. Schweiger M. Kienesberger P. Strauss J.G. Gorkiewicz G. Zechner R. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome.Cell Metab. 2006; 3: 309-319Abstract Full Text Full Text PDF PubMed Scopus (681) Google Scholar, 7Schweiger M. Schreiber R. Haemmerle G. Lass A. Fledelius C. Jacobsen P. Tornqvist H. Zechner R. Zimmermann R. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism.J. Biol. Chem. 2006; 281: 40236-40241Abstract Full Text Full Text PDF PubMed Scopus (519) Google Scholar). Based on these observations, it has that CGI-58 as an for studies have shown that CGI-58 with ATGL through a at the of lipid droplets J.G. of lipolytic protein and in Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google the mechanism by CGI-58 ATGL activity has not the of ATGL and CGI-58 in various and humans with in ATGL J. C. E. J.M. P. A. M. R. The gene encoding adipose triglyceride lipase is in neutral lipid storage disease with Genet. 2007; PubMed Scopus Google with in CGI-58 (2Lefevre C. Jobard F. Caux F. Bouadjar B. Karaduman A. Heilig R. Lakhdar H. Wollenberg A. Verret J.L. Weissenbach J. et al.Mutations in CGI-58, the gene encoding a new protein of the esterase/lipase/thioesterase subfamily, in Chanarin-Dorfman syndrome.Am. J. Hum. Genet. 2001; 69: 1002-1012Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar, 3Igal R.A. Rhoads J.M. Coleman R.A. Neutral lipid storage disease with fatty liver and cholestasis.J. Pediatr. Gastroenterol. Nutr. 1997; 25: 541-547Crossref PubMed Scopus (63) Google Scholar, 4Srebrnik A. Brenner S. Ilie B. Messer G. Dorfman-Chanarin syndrome: morphologic studies and presentation of new cases.Am. J. Dermatopathol. 1998; 20: 79-85Crossref PubMed Scopus (34) Google Scholar, 5Wollenberg A. Geiger E. Schaller M. Wolff H. Dorfman-Chanarin syndrome in a Turkish kindred: conductor diagnosis requires analysis of multiple eosinophils.Acta Derm. Venereol. 2000; 80: 39-43Crossref PubMed Scopus (28) Google Scholar). humans with in ATGL not have but have that are not in with in that CGI-58 as a for or have activity or The carboxyl terminus of CGI-58 an acyltransferase consensus sequence of that is conserved in of CGI-58 from all and that CGI-58 has acyltransferase activity for glycerolipid acceptors. recombinant CGI-58 for acyltransferase activity a of lipid this was in acyltransferase activity of recombinant human CGI-58 G. C. R. CGI-58, the gene for Chanarin-Dorfman of lysophosphatidic Biol. Chem. Full Text Full Text PDF PubMed Scopus Google that complete of the enzyme have studies to of kinetics of the acyltransferase catalyzed by recombinant identification of of CGI-58, and and of the acyltransferase by and have used of the intrinsic fluorescence of tryptophan within CGI-58 to the binding of lipid the of CGI-58 on the metabolism of stored triacylglycerols in fibroblasts from an with and from was from was from was from all and from or and 1-oleoyl lysophosphatidic acid from was from from from and from and The and acid from for protein was from A CGI-58 A. C. A. S. G. R. et A the binding of CGI-58 to lipid droplets in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google was used to the sequence by in two the and and was for with of a CGI-58 with a 6-histidine on the and and at the and of the was into the and of the in with the 6-histidine the CGI-58 fusion protein by this sequence a at the of a was for The CGI-58 was to of The fusion protein was expressed in cells with for at a M. E. F. M. C. and of the and from 2007; PubMed Scopus (28) Google Scholar). for protein at recombinant CGI-58 in a containing pH with or including and or complete by two through a at a cells with in a from an with of by on was to enzyme by The of enzyme activity have from of or from of from the was by at for by of the A of in was to the to a of was by at for at The was a with The was with was from the in a of of with and stored at of protein the of A and for the of of protein the of PubMed Scopus Google with used as a of protein in cells and of of recombinant of structural the of the of PubMed Scopus Google by or was as A. C. A. S. G. R. et A the binding of CGI-58 to lipid droplets in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The fusion protein was with a CGI-58 A. C. A. S. G. R. et A the binding of CGI-58 to lipid droplets in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google by and activity of recombinant CGI-58 was with a of lysophospholipid and neutral lipid acceptors. the recombinant in pH with and lipid lysophosphatidic acid, lysophosphatidyl lysophosphatidyl lysophosphatidyl lysophosphatidyl or or or in a of the was for at activity was also a containing acid and or by the lipids with in to or lipid into a lipid Biol. Google Scholar). by on as the G. R. a lysophosphatidic acid acyltransferase for synthesis on in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). to a and with phosphatidic acid other and by Neutral lipids on with acid as a of the was used to in of for PubMed Scopus Google Scholar). on an an of with from to CGI-58 in pH with addition of various concentrations of oleoyl-CoA, palmitoyl-CoA, arachidonoyl-CoA, 1-oleoyl-lysophosphatidic acid, or at fibroblasts from an with CDS R.A. Coleman R.A. from triacylglycerol to not lipase is defective in neutral lipid storage disease Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, R.A. Coleman R.A. Neutral lipid storage a disorder with in the of Lipid Res. 1998; Full Text Full Text PDF PubMed Google CGI-58, by A. Coleman of and used to the of of CGI-58 in triacylglycerol as R.A. Coleman R.A. from triacylglycerol to not lipase is defective in neutral lipid storage disease Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, R.A. Coleman R.A. Neutral lipid storage a disorder with in the of Lipid Res. 1998; Full Text Full Text PDF PubMed Google Scholar). the of human CGI-58 and by the sequence of the human CGI-58 or the for into the for the the used for of the to and for of in cells. experiments in CDS fibroblasts the of to of CGI-58 and by of by of cells to in CDS cells with acid to at a for to with for CGI-58 or with addition of fatty acids various and cells cells to lipids A of lipid and J. Scholar). by on in acid was and a and of that of the with fatty acid by with of CGI-58, the amino acid for and of CGI-58 and for highly conserved an consensus sequence for glycerolipid acyltransferase activity of the carboxyl terminus of all as as the of and of recombinant CGI-58 for acyltransferase activity a of lipid acceptors. CGI-58 for in vitro studies of enzyme CGI-58 was expressed in Escherichia coli as a fusion protein with two 6-histidine in Recombinant was over a The recombinant was by and in at an of of recombinant that the of the fusion protein expressed in E. coli was to the of CGI-58 in of these at a that from the amino acid sequence for of recombinant CGI-58 that the protein as a not Recombinant was used to acyltransferase activity to a of glycerolipid acceptors. was to containing and lipid including lysophosphatidic acid, lysophosphatidyl lysophosphatidyl lysophosphatidyl lysophosphatidyl and Additional lipid with amino including and The and the lipids by of was and of the of to lipid The was phosphatidic acid lysophosphatidic acid was to the that recombinant CGI-58 has lysophosphatidic acid acyltransferase activity but not the other lipids as substrates the of the neutral lipid including and a of and as substrates with radiolabeled no was in or CGI-58 was for a or by recombinant CGI-58 to containing phosphatidic acid as an and lysophosphatidyl or as of lysophosphatidic acid was used as an to from phosphatidic acid. of was of phosphatidic acid from and 1-oleoyl lysophosphatidic acid increased with time of the to and with increasing of recombinant CGI-58 in a at of the at increased of phosphatidic acid over with at not activity of recombinant CGI-58 was to of the enzyme for at acyltransferase activity at enzyme activity was by at The displayed a pH between 7.0 and at pH The was by the addition of or that these to lipid kinetics lipid substrates to the at concentrations the concentrations of the J.M. of fatty concentrations and and Biol. Chem. Full Text PDF PubMed Google Scholar, concentrations of and Biol. Chem. Full Text PDF PubMed Google Scholar, E. R. The concentrations of lysophosphatidic acid and PubMed Scopus Google Scholar, A of of fatty Biol. Chem. Full Text PDF PubMed Google Scholar, A. The concentrations of fatty and fatty Scopus Google Scholar, J. member a fold with for fatty J. PubMed Scopus Google not used to activity was also by the of and addition of or of phosphatidic acid by or of to acyltransferase activity that was by not of recombinant CGI-58 for of lipids was as with 1-oleoyl-lysophosphatidic acid as the was the for the of phosphatidic acid by oleoyl-CoA palmitoyl-CoA, and substrates for the The of was the of J.M. of fatty concentrations and and Biol. Chem. Full Text PDF PubMed Google Scholar, concentrations of and Biol. Chem. Full Text PDF PubMed Google Scholar, A. The concentrations of fatty and fatty Scopus Google Scholar, J. member a fold with for fatty J. PubMed Scopus Google it is that of CGI-58 and was to of these lipids in the the of the lysophosphatidic acid and have the of of acyltransferase activity was was as a this that CGI-58 is a CoA-dependent lysophosphatidic acid of lysophosphatidic acid with as the acid was a for the acyltransferase acid, acid, or acid The lysophosphatidic acid acyltransferase showed saturation kinetics increasing concentrations of oleoyl-CoA to a of 1-oleoyl-lysophosphatidic acid of the the an with a The was also with respect to 1-oleoyl-lysophosphatidic acid at a of oleoyl-CoA the and of phosphatidic acid was not by the addition of various concentrations of to or to to the not of these lipids was to an for the acyltransferase activity of recombinant CGI-58, as for lysophosphatidic acid. The amino acid sequence of CGI-58 includes tryptophan recombinant CGI-58 intrinsic fluorescence to tryptophan with fluorescence at lipids for the to to CGI-58, and in the fluorescence of fluorescence of CGI-58 was quenched by the addition of for of the lipids the of tryptophan was addition of increasing concentrations of the acid quenched of the tryptophan an of In on the tryptophan fluorescence of recombinant CGI-58 oleoyl-CoA, and quenched of tryptophan fluorescence with of and oleoyl-CoA and 1-oleoyl-lysophosphatidic acid to recombinant CGI-58, a of of of the fluorescence was these that and lysophosphatidic acid to on from a human with CDS R.A. Coleman R.A. from triacylglycerol to not lipase is defective in neutral lipid storage disease Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, R.A. Coleman R.A. Neutral lipid storage a disorder with in the of Lipid Res. 1998; Full Text Full Text PDF PubMed Google that CGI-58 and store excessive triacylglycerol used to of the of CGI-58 on cellular lipid CDS cells with acid to cellular the of of the radiolabeled acid was into with of the in phospholipids and in lipid the of CGI-58 or a control protein to the cells in the of fatty in the metabolism of radiolabeled triacylglycerol of of The of CGI-58 and was by of cells not CGI-58 was expressed in CDS cells, the of radiolabeled triacylglycerol was within of In in cells radiolabeled triacylglycerol by over within of of human or CGI-58, the of triacylglycerol within CDS fibroblasts was to of triacylglycerol in human fibroblasts not In cells CGI-58, a but in the incorporation of radiolabeled into phospholipids was at that was in cells CGI-58 The of radiolabeled released from the hydrolysis of triacylglycerols was into the as fatty acids or not CGI-58 was expressed significantly fatty acid was CGI-58 was The in fatty acids into the is with increased hydrolysis of triacylglycerols in cells an of was to the of cells CGI-58 the the incorporation of radiolabeled fatty acids into radiolabeled fatty acids in the increased not that of radiolabeled fatty acids by a is to incorporation of fatty acids released lipolysis into phospholipids. the enzyme of recombinant CGI-58, a CoA-dependent lysophosphatidic acid acyltransferase CGI-58 acid in a and enzyme but to activity other lysophospholipid or glycerolipid acceptors. CGI-58 displayed saturation kinetics with respect to 1-oleoyl-lysophosphatidic acid and oleoyl-CoA and showed preference for of arachidonoyl-CoA, and oleoyl-CoA, to of The enzyme displayed a slight preference for 1-oleoyl-lysophosphatidic acid over of lysophosphatidic acid with fatty acids in the The enzyme was by and at of recombinant CGI-58 is in with of the of recombinant human CGI-58 for the of lysophosphatidic acid G. C. R. CGI-58, the gene for Chanarin-Dorfman of lysophosphatidic Biol. Chem. Full Text Full Text PDF PubMed Scopus Google but to of enzyme activity by lysophosphatidyl that was in this to lysophosphatidyl binding to CGI-58 through of in the intrinsic tryptophan fluorescence of the in CGI-58 activity. new on the enzyme of CGI-58 and the of CGI-58 on fatty acid between triacylglycerols and phospholipids in human CGI-58 is the lysophospholipid acyltransferase to that is a member of the hydrolase fold family of enzymes The amino acid sequence lacks to characterized within the family of includes of two of the activity of CGI-58, and other lysophospholipid J. Thematic review series: new for an Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar, P. Coleman R.A. of amino acid for the acyltransferase PubMed Scopus Google Scholar, H. on lysophospholipid acyltransferase Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar, H. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, and of and enzymes in triglyceride J. Metab. PubMed Scopus Google Scholar, Coleman R.A. enzymes of triacylglycerol PubMed Scopus Google Scholar). CGI-58 also lacks sequence to the family of includes lysophospholipid acyltransferase and and H. on lysophospholipid acyltransferase Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar, H. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, H. M. R. of membrane family Res. PubMed Scopus Google Scholar, S. C. Thematic review series: enzymes and triacylglycerol Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). CGI-58 lacks the of sequence that these enzymes with it an acyltransferase consensus sequence of and G. C. R. CGI-58, the gene for Chanarin-Dorfman of lysophosphatidic Biol. Chem. Full Text Full Text PDF PubMed Scopus Google shown to important for in P. Coleman R.A. of amino acid for the acyltransferase PubMed Scopus Google Scholar, H. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, A conserved is for glycerolipid acyltransferase 1998; PubMed Google Scholar). is to these amino acids the catalytic The activity of recombinant CGI-58 is to that of other glycerolipid within the various enzyme P. Coleman R.A. of amino acid for the acyltransferase PubMed Scopus Google Scholar, H. M. R. of membrane family Res. PubMed Scopus Google of these enzymes have not to The enzyme with the sequence to CGI-58 is has to have and activity and to for signaling lipids through and a role for in this Biol. Chem. 2006; 281: Full Text Full Text PDF PubMed Scopus Google Scholar). from multiple have the conserved carboxyl terminal consensus CGI-58, also have conserved GXSXG consensus the nucleophilic serine residue for lipase activity. CGI-58 displayed tryptophan fluorescence that was quenched by the addition of of tryptophan fluorescence was used to for of in the and for 1-oleoyl-lysophosphatidic acid. of intrinsic tryptophan fluorescence the that the two lipids to of the active of the concentrations of lysophosphatidic acid to tryptophan in the of oleoyl-CoA. of tryptophan fluorescence lipid concentrations the concentrations for lipids to the of of The of lipid binding to recombinant CGI-58 was that the protein not have multiple binding for these with of the protein from a as a these that CGI-58 is active as a of the of CGI-58 is to the of tryptophan to binding at this it is of tryptophan fluorescence is to the of substrates to tryptophan or in the protein Expression of human CGI-58 in human CDS fibroblasts that CGI-58 and store excessive triacylglycerols excessive triacylglycerol storage and increased the of of radiolabeled The of the released fatty acids into the of CGI-58 significantly increased incorporation of fatty acids into cellular phospholipids. The of CGI-58 on increased of triacylglycerol in CDS fibroblasts was (6Lass A. Zimmermann R. Haemmerle G. Riederer M. Schoiswohl G. Schweiger M. Kienesberger P. Strauss J.G. Gorkiewicz G. Zechner R. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome.Cell Metab. 2006; 3: 309-319Abstract Full Text Full Text PDF PubMed Scopus (681) Google the of fatty acids released lipolysis was not for these cells. slight in cellular triacylglycerol CGI-58 was in cells, and cells J.M. S. A. CGI-58 the of cytoplasmic triglyceride for in Lipid Res. 2007; 48: Full Text Full Text PDF PubMed Scopus Google In to with CDS was expressed in radiolabeled triacylglycerols but was no in radiolabeled fatty acid incorporation into phospholipids J.M. S. A. CGI-58 the of cytoplasmic triglyceride for in Lipid Res. 2007; 48: Full Text Full Text PDF PubMed Scopus Google Scholar). for these are cells CGI-58 P. M. cell lipid droplets to in membrane Biol. Chem. Full Text Full Text PDF PubMed Scopus Google and of CGI-58 in cells have J.M. S. A. CGI-58 the of cytoplasmic triglyceride for in Lipid Res. 2007; 48: Full Text Full Text PDF PubMed Scopus Google Scholar). the of radiolabeled fatty acids into phospholipids CGI-58 was or fatty acids hydrolysis of triacylglycerols R.A. P. Coleman R.A. synthesis of and but not of fatty acid into for of J. 1997; PubMed Scopus Google Scholar, Coleman R.A. Expression and of recombinant and by and Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, Coleman R.A. and are in in liver and Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). studies in CDS cells have that are no major in the or of phospholipids in of CDS fibroblasts R.A. Coleman R.A. from triacylglycerol to not lipase is defective in neutral lipid storage disease Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, R.A. Coleman R.A. Neutral lipid storage a disorder with in the of Lipid Res. 1998; Full Text Full Text PDF PubMed Google CGI-58 not a major role in cellular synthesis or the of CGI-58 in cells and is A. C. A. S. G. R. et A the binding of CGI-58 to lipid droplets in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google the of humans with CDS that CGI-58 plays a role in triacylglycerol homeostasis in many tissues. that CGI-58 at the lipid droplet A. C. A. S. G. R. et A the binding of CGI-58 to lipid droplets in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, S. CGI-58 with perilipin and is to lipid of CGI-58 in Chanarin-Dorfman Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, E. H. F. CGI-58 lipolysis on lipid droplets but is not in the of lipid droplets by Lipid Res. 2007; 48: Full Text Full Text PDF PubMed Scopus Google to fatty acids released from hydrolysis of triacylglycerols into as a of of neutral lipid the of CGI-58 for arachidonoyl-CoA that CGI-58 a role in for the of signaling the of phosphatidic acid or of lysophosphatidic acid through the enzyme activity of CGI-58 an important role in signaling of these CGI-58 plays an important role in triacylglycerol hydrolysis catalyzed by ATGL (6Lass A. Zimmermann R. Haemmerle G. Riederer M. Schoiswohl G. Schweiger M. Kienesberger P. Strauss J.G. Gorkiewicz G. Zechner R. Adipose triglyceride lipase-mediated lipolysis of cellular fat stores is activated by CGI-58 and defective in Chanarin-Dorfman Syndrome.Cell Metab. 2006; 3: 309-319Abstract Full Text Full Text PDF PubMed Scopus (681) Google Scholar, 7Schweiger M. Schreiber R. Haemmerle G. Lass A. Fledelius C. Jacobsen P. Tornqvist H. Zechner R. Zimmermann R. Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism.J. Biol. Chem. 2006; 281: 40236-40241Abstract Full Text Full Text PDF PubMed Scopus (519) Google Scholar, A. C. C. A. J. J. R. M. et of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). is this role of CGI-58 requires lysophosphatidic acid acyltransferase activity or is a by a between CGI-58 and the lipase J.G. of lipolytic protein and in Biol. Chem. 2007; Full Text Full Text PDF PubMed Scopus Google Scholar). of lysophosphatidic acid acyltransferase activity in recombinant human CGI-58 and G. C. R. CGI-58, the gene for Chanarin-Dorfman of lysophosphatidic Biol. Chem. Full Text Full Text PDF PubMed Scopus Google that cause CDS that CGI-58 two CGI-58 with at these is not to lipid droplets S. CGI-58 with perilipin and is to lipid of CGI-58 in Chanarin-Dorfman Biol. Chem. Full Text Full Text PDF PubMed Scopus Google in CGI-58 that of the protein CGI-58 in maintenance of triacylglycerol Additional is to of CGI-58 in lipid metabolism and The A. Coleman for the of the CDS cell and for and adipose triglyceride lipase Chanarin-Dorfman syndrome acid