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The differential effect of eicosapentaenoic acid and oleic acid on lipid synthesis and VLDL secretion in rabbit hepatocytes
Author(s) -
Benner Kent G.,
Sasaki Anna,
Gowen Dale R.,
Weaver Alice,
Connor William E.
Publication year - 1990
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02537160
Subject(s) - oleic acid , triglyceride , very low density lipoprotein , phospholipid , fatty acid , hepatocyte , eicosapentaenoic acid , biochemistry , chemistry , medicine , biology , polyunsaturated fatty acid , lipoprotein , cholesterol , in vitro , membrane
The suppression of plasma very low density lipoprotein (VLDL) triglyceride levels by dietary fish oils rich in polyunsaturated n−3 fatty acids has been attributed to decreased hepatic VLDL secretion. To investigate the effect of n−3 fatty acids on lipid metabolism and VLDL secretion in a tissue culture system, we incubated rabbit hepatocytes with oleic acid and eicosapentaenoic acid (EPA) and examined [ 3 H]glycerol and [ 14 C]fatty acid incorporation into hepatocyte triglyceride and phospholipid and into media VLDL. Glycerol incorporation studies showed that EPA failed to stimulate VLDL triglyceride secretion from hepatocytes as occurred with oleic acid (P<0.05). Oleic acid preferentially enhanced hepatocyte triglyceride synthesis while EPA stimulated significantly phospholipid synthesis (P<0.01). Varying the relative concentrations of oleic acid and EPA at a constant total fatty acid concentration corroborated preferential triglyceride synthesis from oleic acid. Synthesis shifted predominantly to phospholipids with increasing concentrations of EPA and lower levels of oleic acid. Incorporation of the [ 14 C]fatty acids (800 μM) followed similar patterns: 87% of [ 14 C]oleic acid was incorporated into hepatocyte triglyceride and 44% of [ 14 C]EPA was assimilated in hepatocyte phospholipid (p<0.001). Fatty acids at trace concentrations (53 nM) showed a more divergent pattern of lipid incorporation: 60% of [ 14 C]oleic acid was incorporated into triglyceride while 91% of [ 14 CEPA was incorporated into phospholipid (p<0.001). We conclude that in primary rabbit hepatocyte culture, which appears to be a useful model to study lipid metabolism and VLDL secretion, EPA is avidly incorporated into phospholipid while oleic acid predominantly becomes esterified in triglyceride. In addition, EPA, unlike oleic acid, fails to stimulate hepatocyte VLDL secretion. These divergent effects on hepatocyte lipid metabolism are, at least in part, likely to be responsible for fish oil induced suppression of plasma triglycerides.