PALMITIC ACID AND LINOLEIC-ACID METABOLISM IN CACO-2 CELLS - DIFFERENT TRIGLYCERIDE SYNTHESIS AND LIPOPROTEIN SECRETION

Polarized monolayers of intestinal Caco-2 cells were used to study the effects of saturated palmitic acid (16:0) and polyunsaturated linolei c acid (18:2) on triglyceride synthesis and lipoprotein secretion. Mon olayers were incubated for 24 h, at the apical or lumenal side, with p almitic acid (16:0) or linoleic acid (18:2) in physiological concentra tions. Incubation with 1.0 mM 16:0 or 18:2 resulted in differences in the composition and amount of secreted lipoproteins. Radiolabeled lipi ds in the lipoproteins secreted during incubation with 18:2 were found in the chylomicron/VLDL (very low density lipoprotein) density wherea s with 16:0 the secreted lipoproteins were in the intermediate density /low density lipoprotein (IDL/LDL) density range. More triglyceride wa s secreted into the (basolateral) medium during incubation with 1.0 mM 18:2 (41 +/- 12% of total triglyceride synthesized) than with 1.0 mM 16:0 (18 +/- 3% of total). The biochemical findings correlate with con spicuous morphological changes in the cells in the presence of 16:0, b ut not 18:2. Increasing concentrations of 16:0 (0.1-1.0 mM) caused gra dual accumulation of intracellular membrane. Microvilli became strongl y reduced in number. With 1.0 mM palmitic acid we found an increased i ncorporation of [1(-14)C]palmitic acid into phosphatidic acid (14.8% o f total incorporation into phospholipid with 16:0 vs. < 0.5% with 18:2 ) and diacylglycerol (12.5% with 16:0 vs. 0.5% with 18:2) and the amou nt of intracellular phospholipid doubled. The morphological changes we re completely reversed-after 24 h with 1.0 mM 18:2. We conclude from o ur results that, compared to 18:2, 16:0 is not efficiently incorporate d into triglycerides. 16:0 is incorporated into cellular phospholipids in a greater proportion than 18:2, causing accumulation of intracellu lar phospholipid and the precursors phosphatidic acid and diacylglycer ol. Different processing of 18:2 and 16:0 by Caco-2 cells resulted in profound differences in triglyceride synthesis and lipoprotein composi tion and secretion.