title: Myristic acid-rich fat raises plasma LDL by stimulating LDL production without affecting fractional clearance in gerbils fed a cholesterol-free diet.
abstract: The imbalance that develops between low-density lipoprotein (LDL) production and clearance during saturated fat consumption is responsible for expanding the circulating LDL pool. To assess the imbalance attributable to fatty acids alone, i.e., without the interaction of dietary cholesterol, the most fat-sensitive species available (the gerbil) was challenged with either a 12:0+14:0 rich-fat (high coconut, low safflower) or high 18:2 (high safflower, low coconut) fat for 4-5 wks. The plasma lipoprotein cholesterol profile, including lipoprotein composition, particle size and 125I-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 mmol/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), the high-density lipoprotein (HDL2) fraction increased the most (27 vs. 79 mg/100 mL; 0.7 +/- 0.02 vs. 2.0 +/- 0.1 mmol/L, P < 0.05) with minimal 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 rate did not differ between gerbils with these extreme fat intakes, implicating overproduction and not reduced clearance as the primary consideration in LDL expansion. Thus SFA-induced cholesterolemia can be severe in the absence of dietary cholesterol with a greater impact on high-density lipoprotein than LDL and without an appreciable role attributed to LDL clearance (receptors).
authors.affiliation: Foster Biomedical Research Laboratory, Brandeis University, Waltham, MA 02254, USA.
authors.forename: T
authors.initials: T
authors.lastname: Hajri
authors.forename: P
authors.initials: P
authors.lastname: Khosla
authors.forename: A
authors.initials: A
authors.lastname: Pronczuk
authors.forename: K C
authors.initials: KC
authors.lastname: Hayes
mesh_terms: D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D004041:Dietary Fats / Q000494:pharmacology*; D005223:Fats / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D005849:Gerbillinae; D008055:Lipids / Q000097:blood / Q000737:chemistry; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D019814:Myristic Acid / Q000494:pharmacology*; D011973:Receptors, LDL / Q000378:metabolism
chemical_list: D002791:Cholesterol, Dietary; D004041:Dietary Fats; D005223:Fats; D005227:Fatty Acids; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D019814:Myristic Acid