MYRISTIC ACID-RICH FAT RAISES PLASMA LDL BY STIMULATING LDL PRODUCTION WITHOUT AFFECTING FRACTIONAL CLEARANCE IN GERBILS FED A CHOLESTEROL-FREE DIET

The imbalance that develops between low-density lipoprotein (LDL) prod uction and clearance during saturated fat consumption is responsible f or expanding the circulating LDL pool. To assess the imbalance attribu table to fatty acids alone, i.e., without the interaction of dietary c holesterol, the most fat-sensitive species available (the gerbil) was challenged with either a 12:0+14:0 rich-fat (high coconut, law safflow er) or high 18:2 (high safflower, low coconut) fat for 4-5 wks. The pl asma lipoprotein cholesterol profile, including lipoprotein compositio n, particle size and I-125-LDL turnover were measured. Although total plasma cholesterol (TC) was threefold higher with saturated fatty acid (SFA) feeding (230 vs. 70 mg/100 mL; 5.9 +/- 0.1 vs. 1.8 +/- 0.05 mmo l/L, P < 0.0001) and LDL cholesterol (LDL-C) was fivefold greater (10 vs. 54 mg/100 mL; 0.26 +/- 0.02 vs. 1.4 +/- 0.02 mmol/L, P < 0.001), t he high-density lipoprotein (HDL2) fraction increased the most (27 vs. 79 mg/100 mt; 0.7 +/- 0.02 vs. 2.0 +/- 0.1 mmol/L, P < 0.05) with min imal HDL3 (NS) difference (16 vs. 26 mg/100 mL; 0.43 +/- 0.08 vs. 0.7 +/- 0.05 mmol/L). Particle composition and size did not differ between groups. LDL kinetic analyses revealed that the fractional catabolic r ate did not differ between gerbils with these extreme fat intakes, imp licating overproduction and not reduced clearance as the primary consi deration in LDL expansion. Thus SPA-induced cholesterolemia can be sev ere in the absence of dietary cholesterol with a greater impact on hig h-density lipoprotein than LDL and without an appreciable role attribu ted to LDL clearance (receptors).