title: Saturated non-esterified fatty acids stimulate de novo diacylglycerol synthesis and protein kinase c activity in cultured aortic smooth muscle cells.
abstract: OBJECTIVE
  Insulin resistance is linked with a cluster of multiple risk factors and excessive acceleration of atherosclerosis. The underlying mechanism is not, however, fully understood.
  
  
  METHODS
  To determine the link between insulin resistance and altered vascular function, we focused on the effect of various non-esterified fatty acids on diacylglycerol-protein kinase C pathway and mitogen-activated protein kinase activity in cultured aortic smooth muscle cells.
  
  
  RESULTS
  Incubation of the cells with saturated non-esterified fatty acids (200 micromol/l) for 24 h, such as palmitate or stearate, induced a significant increase in diacylglycerol concentrations by about fivefold or eightfold, respectively, whereas oleate induced a slight increase in diacylglycerol concentrations by 1.8-fold and arachidonate induced none. In addition, the increased diacylglycerol concentrations induced by palmitate were completely restored to control concentrations by triacsin C, acyl-CoA synthetase inhibitor. These results suggest that saturated non-esterified fatty acids may increase diacylglycerol concentrations through de novo pathway by stepwise acylation. In parallel with the increased diacylglycerol, incubation of the cells with saturated non-esterified fatty acids significantly induced the activation of protein kinase C and mitogen-activated protein kinase. The palmitate-induced increase in mitogen-activated protein kinase activity was restored to control concentrations by GF109203X (5 x 10(-7) mol/l), a specific protein kinase C inhibitor, suggesting a protein kinase C-dependent activation of mitogen-activated protein kinase.
  
  
  CONCLUSIONS
  Saturated non-esterified fatty acids induced an increase in de novo diacylglycerol synthesis and subsequent activation of protein kinase C and mitogen-activated protein kinase in cultured aortic smooth muscle cells. This could contribute to the altered vascular functions in the insulin resistant state.
authors.affiliation: Graduate School of Medical Sciences, Kyushyu University, Fukuoka, Japan.
authors.forename: H Y
authors.initials: HY
authors.lastname: Yu
authors.forename: T
authors.initials: T
authors.lastname: Inoguchi
authors.forename: M
authors.initials: M
authors.lastname: Kakimoto
authors.forename: N
authors.initials: N
authors.lastname: Nakashima
authors.forename: M
authors.initials: M
authors.lastname: Imamura
authors.forename: T
authors.initials: T
authors.lastname: Hashimoto
authors.forename: F
authors.initials: F
authors.lastname: Umeda
authors.forename: H
authors.initials: H
authors.lastname: Nawata
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016718:Arachidonic Acid / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D003066:Coenzyme A Ligases / Q000037:antagonists & inhibitors; D004075:Diglycerides / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology; D007700:Kinetics; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D013229:Stearic Acids / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014226:Triazenes / Q000494:pharmacology
chemical_list: D004075:Diglycerides; D004791:Enzyme Inhibitors; D005230:Fatty Acids, Nonesterified; D007211:Indoles; D008301:Maleimides; D013229:Stearic Acids; D014226:Triazenes; D016718:Arachidonic Acid; D019301:Oleic Acid; D019308:Palmitic Acid; C031183:stearic acid; C034613:triacsin C; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D003066:Coenzyme A Ligases; C070515:bisindolylmaleimide I; D013755:Tetradecanoylphorbol Acetate