title: Attenuated secretion of very low density lipoproteins from McA-RH7777 cells treated with eicosapentaenoic acid is associated with impaired utilization of triacylglycerol synthesized via phospholipid remodeling.
abstract: In McA-RH7777 cells stably expressing human apolipoprotein (apo) B100, treatment with oleic acid (18:1(n-9)) promoted whereas treatment with eicosapentaenoic acid (EPA, 20:5(n-3)) attenuated assembly and secretion of VLDL. Under conditions where the cells were cultured in the presence of 20% serum, EPA (0.4 mM) had marginal effect on the secretion of total apoB100 (determined by pulse-chase analysis) but decreased (by 50%) secretion of triacylglycerol (TG), indicating that the inhibitory effect of EPA was exerted primarily on TG-rich VLDL. Analysis of phospholipid mass and species by tandem mass spectrometry showed increased phosphatidylethanolamine (PE) in EPA-treated cells, the increase was significant in the distal Golgi membranes (by 170%) and endoplasmic reticulum (by 116%). Lipid pulse-chase studies showed a major distinction between phospholipid species containing 20:5(n-3) and 18:1(n-9), which in turn was associated with distinct compartmentalization of TG containing 20:5(n-3) or 18:1(n-9) between cytosol and microsomes and their recruitment during VLDL assembly. Thus, 18:1-TG was secreted as VLDL but 20:5-TG was not. These results suggest that EPA attenuation of VLDL secretion is associated with impaired utilization of TG derived from phospholipid remodeling.
authors: Lipoprotein and Atherosclerosis Research Group, University of Ottawa Heart Institute, Ottawa, Canada K1Y 4W7.
authors: Khai
authors: K
authors: Tran
authors: Fengcheng
authors: F
authors: Sun
authors: Zheng
authors: Z
authors: Cui
authors: Gro
authors: G
authors: Thorne-Tjomsland
authors: Carly
authors: C
authors: St Germain
authors: Louis R
authors: LR
authors: Lapierre
authors: Roger S
authors: RS
authors: McLeod
authors: James C
authors: JC
authors: Jamieson
authors: Zemin
authors: Z
authors: Yao