Stearic acid modifies very low density lipoprotein lipid composition and particle size differently from shorter-chain saturated fatty acids in cultured rat hepatocytes.

Stearic acid as compared to myristate, palmitate, or oleate is poorly incorporated into triacylglycerol, a major lipid component of very low density lipoprotein (VLDL). The present study investigated the effects of these fatty acids on VLDL metabolism in cultured rat hepatocytes. All fatty acids stimulated [2-3H] glycerol incorporation into VLDL lipids and secretion of [3H]-labeled VLDL by hepatocytes. However, the rate of [3H]-labeled VLDL secretion in the presence of nonlabeled stearate (12.8 +/- 0.7 pmol/mg protein/4 h) was 46, 59, and 22% of that observed for those treated with myristate, palmitate, and oleate, respectively. [1-14C]Stearate as a substrate was also less effective than other labeled fatty acids to be incorporated into VLDL lipids. Of total VLDL lipids synthesized from [1-14C] stearate, triacylglycerol accounted for 78% as compared to 88-97% of that derived from palmitate, myristate, and oleate. The amounts of apoB100 and apoB48 were the same in hepatocytes treated with or without exogenous fatty acids. Similarly, the rate of apoB synthesis from [35S] methionine was not affected by exogenous fatty acids. The treatment of cells with various saturated fatty acids increased the particle size of VLDL to different extents. The largest particles of VLDL, with a mean diameter of 79.3 +/- 11.9 nm, were seen in the cells treated with stearate, followed by those treated with palmitate and myristate (45.5 +/- 9.8 and 38.6 +/- 6.8 nm, diameter, respectively). Clearly, hepatocytes treated with stearate secrete less VLDL and produce larger VLDL particles than those treated with shorter-chain saturated fatty acids.