Effects of eicosapentaenoic and docosahexaenoic acids on apoprotein B mRNA and secretion of very low density lipoprotein in HepG2 cells.

Wong, Sue; Fisher, Edward A.; Marsh, Julian B.

doi:10.1161/01.atv.9.6.836

Cited by 92 publications

(53 citation statements)

References 20 publications

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“…Evidence was provided to suggest that the n-3 fatty acid impaired the assembly or secretion of very low density lipoprotein particles by inhibiting the secretion of newly synthesized apolipoprotein B (apo B). A decrease in the secretion of newly synthesized apo B by eicosapentaenoic acid was also observed by Wong et al 6 in HepG2 cells.…”

supporting

confidence: 74%

“…This supports a previous observation by Dashti et al 19 The incorporation of labeled methionine into cellular or medium apo B, however, was not increased by oleate. Lang and Davis 5 and Wong et al 6 found similar results in cultured hepatocytes. Thus, in response to an influx of oleic acid, an increase in the rate of apo B synthesis is not required by CaCo-2 cells or liver cells to transport triglycerides or apo B.…”

Section: Discussionmentioning

confidence: 68%

“…A 48-hour incubation period was chosen for this study because shorter periods of incubation were thought to be too short to detect changes in mRNA abundance. 6 Pullinger et al 10 estimated the half-life of apo B mRNA in HepG2 cells to be 16 hours. Wong et al 6 failed to detect changes in apo B mRNA abundance by eicosapentaenoic acid after 3 hours of incubation with HepG2 cells, a duration probably much too short to observe changes in apo B mRNA levels.…”

Section: Discussionmentioning

confidence: 99%

“…6 Pullinger et al 10 estimated the half-life of apo B mRNA in HepG2 cells to be 16 hours. Wong et al 6 failed to detect changes in apo B mRNA abundance by eicosapentaenoic acid after 3 hours of incubation with HepG2 cells, a duration probably much too short to observe changes in apo B mRNA levels. Lang and Davis 5 in their study did not measure apo B message levels.…”

Section: Discussionmentioning

confidence: 99%

“…Aliquots from cell and basolateral media containing 5xlO 6 TCA-precipitable counts were precleared of nonspecific counts by incubation with 0.2 ml IgGsorb (10% wt/vol) on a tube rocker for 1 hour at 4°C. This was followed by centrifugation for 5 minutes in a refrigerated microfuge.…”

Section: Immunoprecipitation Of Apolipoprotein B and Apolipoprotein A-imentioning

confidence: 99%

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Apolipoprotein B mRNA abundance is decreased by eicosapentaenoic acid in CaCo-2 cells. Effect on the synthesis and secretion of apolipoprotein B.

Murthy

Albright

Mathur

et al. 1992

Arterioscler Thromb

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The regulation of apolipoprotein B (apo B) metabolism by eicosapentaenoic acid was investigated in CaCo-2 cells. Cells cultured on semipermeable membranes that separated an upper from a lower well were incubated for 48 hours with albumin alone or 1 mM eicosapentaenoic acid or oleic acid attached to albumin (4:1, mol/mol). Compared with cells incubated with oleic acid, cells incubated with eicosapentaenoic acid synthesized and secreted less [ 3 H]glycerol-Iabeled triglycerides. Although both fatty acids increased cellular triglyceride mass compared with control cells, less triglycerides accumulated in cells incubated with the n-3 fatty acid. The secretion of triglyceride and apo B mass by cells incubated with eicosapentaenoic acid was less than that observed by cells incubated with oleate. The amount of apo B mass within cells, however, was not altered by either of the fatty acids and was similar to amounts found in control cells. Apo B mRNA abundance was decreased fourfold in cells exposed for 48 hours to eicosapentaenoic acid. In contrast, in cells incubated with oleic acid, apo B mRNA levels were not significantly altered. Pulse-chase experiments were performed to investigate the regulation of apo B synthesis and degradation by the fatty acids. In cells incubated with eicosapentaenoic acid, the synthesis and basolateral secretion of newly synthesized apo B-100 and apo B-48 were significantly less compared with control cells or cells incubated with oleic acid. In contrast, the synthesis and secretion of newly synthesized apo B in cells exposed to oleic acid were similar to control cells. Rates of apo A-I synthesis were similar in cells incubated with either of the fatty acids. Compared with control cells and cells incubated with eicosapentaenoic acid, the residence time of labeled apo B in cells incubated with oleic acid was prolonged. The percentage of newly synthesized apo B that was degraded was less in cells incubated with oleic acid. In contrast, residence times and the percentages of apo A-I and apo B-48 degraded were similar in control cells and cells incubated with the fatty acids. Thus, in CaCo-2 cells, compared with the effects of oleic acid, eicosapentaenoic acid impairs triglyceride transport in part by inhibiting apo B synthesis and secretion. The inhibition of apo B synthesis by eicosapentaenoic acid may be related to a decrease in gene transcription or a decrease in mRNA stability, as apo B mRNA levels were significantly decreased in cells incubated with this fatty acid. In contrast, compared with control cells, oleic acid did not increase either the rate of synthesis or the secretion of newly synthesized apo B-100. The monoenoic fatty acid did, however, delay the disappearance of apo B-100 in the cell and decrease the percentage of newly synthesized apo B-100 that was degraded. Because apo B mass secretion was increased by oleic acid, the results suggest that in intestinal cells, there is a preformed pool of apo B that is used for the transport of triglycerides into the lymph. ( T he predominant...

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supporting

confidence: 74%

Section: Discussionmentioning

confidence: 68%