title: Endothelial acyl-CoA synthetase 1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment.
abstract: OBJECTIVE
  Saturated fatty acids, such as palmitic and stearic acid, cause detrimental effects in endothelial cells and have been suggested to contribute to macrophage accumulation in adipose tissue and the vascular wall, in states of obesity and insulin resistance. Long-chain fatty acids are believed to require conversion into acyl-CoA derivatives to exert most of their detrimental effects, a reaction catalyzed by acyl-CoA synthetases (ACSLs). The objective of this study was to investigate the role of ACSL1, an ACSL isoform previously shown to mediate inflammatory effects in myeloid cells, in regulating endothelial cell responses to a saturated fatty acid-rich environment in vitro and in vivo.
  
  
  RESULTS
  Saturated fatty acids caused increased inflammatory activation, endoplasmic reticulum stress, and apoptosis in mouse microvascular endothelial cells. Forced ACSL1 overexpression exacerbated the effects of saturated fatty acids on apoptosis and endoplasmic reticulum stress. However, endothelial ACSL1 deficiency did not protect against the effects of saturated fatty acids in vitro, nor did it protect insulin-resistant mice fed a saturated fatty acid-rich diet from macrophage adipose tissue accumulation or increased aortic adhesion molecule expression.
  
  
  CONCLUSIONS
  Endothelial ACSL1 is not required for inflammatory and apoptotic effects of a saturated fatty acid-rich environment.
authors.affiliation: Departments of Pathology, University of Washington, Seattle WA, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Oscar
authors.initials: O
authors.lastname: Gonzalez
authors.forename: Xia
authors.initials: X
authors.lastname: Shen
authors.forename: Shelley
authors.initials: S
authors.lastname: Barnhart
authors.forename: Farah
authors.initials: F
authors.lastname: Kramer
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Kanter
authors.forename: Anuradha
authors.initials: A
authors.lastname: Vivekanandan-Giri
authors.forename: Kyoichiro
authors.initials: K
authors.lastname: Tsuchiya
authors.forename: Priya
authors.initials: P
authors.lastname: Handa
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Pennathur
authors.forename: Francis
authors.initials: F
authors.lastname: Kim
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Coleman
authors.forename: Jean E
authors.initials: JE
authors.lastname: Schaffer
authors.forename: Karin E
authors.initials: KE
authors.lastname: Bornfeldt
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D017209:Apoptosis; D002417:Cattle; D002478:Cells, Cultured; D003066:Coenzyme A Ligases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress; D042783:Endothelial Cells / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D004789:Enzyme Activation; D005227:Fatty Acids / Q000378:metabolism*; D007249:Inflammation / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D007333:Insulin Resistance; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D010171:Palmitoyl Coenzyme A / Q000378:metabolism; D034622:RNA Interference; D013997:Time Factors; D014162:Transfection; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D000214:Acyl Coenzyme A; D005227:Fatty Acids; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D010171:Palmitoyl Coenzyme A; C017725:stearoyl-coenzyme A; D048031:JNK Mitogen-Activated Protein Kinases; C544400:ACSL1 protein, mouse; D003066:Coenzyme A Ligases