Fish oil fatty acids impair VLDL assembly and/or secretion by cultured rat hepatocytes.

Ca Lang,Ra Davis

doi:10.1016/s0022-2275(20)42272-2

Abstract

We determined the effect of the two major fish oil fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on VLDL assembly and secretion by cultured rat hepatocytes. The incorporation of [3H]glycerol into total triglyceride (cell plus media) was stimulated eight-fold when hepatocytes were incubated for 2 h with 1 mM EPA, DHA, or oleic acid (OA), suggesting that fish oil fatty acids stimulate hepatic triglyceride synthesis to an extent similar to OA. In contrast, mass quantitation of secreted triglyceride showed impaired triglyceride secretion with EPA and DHA compared to OA. During a 42-h time course, cells stimulated with EPA and DHA progressively accumulated triglyceride compared to cells stimulated with OA. To determine whether fish oil fatty acids impair very low density lipoprotein (VLDL) secretion, cells were labeled with [35S]methionine and the secretion of de novo synthesized apoB was measured. Compared to OA, EPA and DHA significantly impaired the secretion of both molecular weight forms of apoB. The cellular content of apoB was not altered by any of the fatty acids. The concordant decrease in the secretion of both triglyceride and apoB suggests that fish oil fatty acids impair VLDL assembly and/or secretion.

Highlights

We determined the effect of the two major fish oil fatty acids, eicosapemtaenoic acid (EPA) and docosahexaenoic acid (DHA), on very low density lipoprotein (VLDL) assembly and secretion by cultured rat hepatocytes
During 2-h incubations all three fatty acids (EPA, DHA, and oleic acid (OA)) stimulated the accumulation of cell plus media ['Hltriglyceride to a similar extent (Fig. 1A) suggesting that there is no difference between fish oil fatty acids and OA in their ability to stimulate triglyceride synthesis
Cells stimulated with OA secreted 34 - 57% more ['Hltriglyceride than cells stimulated with EPA or DHA, respectively

Summary

Introduction

We determined the effect of the two major fish oil fatty acids, eicosapemtaenoic acid (EPA) and docosahexaenoic acid (DHA), on VLDL assembly and secretion by cultured rat hepatocytes. Since EPA and DHA were not as effective as oleic acid (OA) in stimulatingtriglyceridesynthesis,the impairment of VLDL triglycerided o n was attributed to inhibitionof triglyceride synthesis [6,7] This hypothesis is supported by data suggesting that fish oil fatty acids decrease the activity of two enzymes involved in triglyceride synthesis: diacylglycerol acyl transferase [8] and phosphatidate phosphohydrolase [9]. To determine whether fish oil fatty acids impair the assembly and/or secretionof VLDL particles, we studied the effects of EPA and DHA on the assembly and secretion of VLDL by cultured rat hepatocytes. The results show that fuh oil fatty acids impair VLDL assembly or secretion through a mechanism not involving decreased triglyceride synthesis or availability

Methods

Results

Conclusion