Effects of eicosapentaenoic and docosahexaenoic acids on apoprotein B mRNA and secretion of very low density lipoprotein in HepG2 cells.
Oleic acid (18:1n-9, OA), docosahexaenoic acid (22:6n-3, DHA), or eicosapentaenoic acid (20:5n-3, EPA) was added to HepG2 cells at a concentration of 1 mM in a 5:1 or 2:1 molar complex with bovine serum albumin (BSA), and this was incubated for 3 hours. The incorporation of 3H-glycerol into cellular and medium triglyceride (TG), and the mass of TG were measured. The effects of these fatty acids on the secretion of very low density lipoprotein (VLDL) apolipoprotein B (apo B) were estimated from the incorporation of 3H-leucine into the medium apo B in comparison to cells incubated with fatty acid-poor albumin. The secretion of human albumin by the cells was also estimated by immunochemical precipitation of the labeled albumin. In addition, the intracellular levels of apo B messenger ribonucleic acid (mRNA) were measured by the dot-blot hybridization technique. Relative to control cells incubated with BSA, OA (complexed to BSA at a 5:1 molar ratio) stimulated TG synthesis and secretion sevenfold. Compared to OA, EPA was 24% less effective for both processes, whereas DHA inhibited only the secretion of TG (-43%). The secretion of VLDL apo B was not affected by OA, but was decreased 31% by EPA and 54% by DHA. When the molar ratio of fatty acid complexed to albumin was changed to 2:1, similar results were obtained with respect to TG production. The levels of apo B mRNA relative to actin mRNA were not significantly altered by any of the fatty acids.(ABSTRACT TRUNCATED AT 250 WORDS)
Wong
S H
SH
Department of Physiology and Biochemistry, Medical College of Pennsylvania, Philadelphia 19129.
Fisher
E A
EA
Marsh
J B
JB
D000418:Albumins / Q000378:metabolism; D001055:Apolipoproteins B / Q000235:genetics*; D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000378:metabolism / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000418:Albumins; D001055:Apolipoproteins B; D008079:Lipoproteins, VLDL; D009829:Oleic Acids; D010743:Phospholipids; D014280:Triglycerides; D004281:Docosahexaenoic Acids; D019301:Oleic Acid; D015118:Eicosapentaenoic Acid