TETRADECYLTHIOACETIC ACID (A 3-THIA FATTY-ACID) DECREASES TRIACYLGLYCEROL SECRETION IN CACO-2 CELLS

The effects of the hypolipidemic fatty acid analogue tetradecylthioace tic acid (TTA) on synthesis and secretion of lipoproteins in CaCo-2 ce lls were studied. Radiolabeled tetradecylthioacetic acid was absorbed and metabolized as efficiently as oleic acid, although a discrepancy i n the metabolic fate,was evident. Whereas tetradecylthioacetic acid wa s incorporated into cell-associated triacylglycerol to the same extent as normal fatty acids (e.g., oleic acid and palmitic acid), the amoun t of triacylglycerol secreted from cells incubated with tetradecylthio acetic acid was 8 to 10 times lower than the amount secreted from cell s incubated with palmitic acid and oleic acid, respectively. On the ot her hand, there was an enhanced incorporation of tetradecylthioacetic acid into cell-associated and secreted phospholipids. Despite incorpor ation of tetradecylthioacetic acid into cellular triacylglycerol, unli ke oleic acid, tetradecylthioacetic acid did not stimulate production of triacylglycerol-rich particles. Ultracentrifugation of basolateral media from cells incubated with tetradecylthioacetic acid revealed low amounts of triacylglycerol in the triacylglycerol-rich fraction (rho < 1.006 g/ml), suggesting secretion of lipoproteins with a higher dens ity than chylomicrons. However, the present study shows that the stimu lated triacylglycerol secretion caused by oleic acid was inhibited in the presence of TTA. The decreased rate of triacylglycerol secretion f rom these cells was not accompanied by a stimulation of fatty acid oxi dation. Based on these findings, we therefore suggest that tetradecylt hioacetic acid mainly affects secretion of lipoproteins in CaCo-2 cell s.