Dietary n-3 polyunsaturated fat increases the fractional catabolic rate of medium-sized HDL particles in African green monkeys.
We have previously described a novel pathway for the metabolism of HDL subfractions in which small [2 apolipoprotein (apoA-I) molecules per particle] HDL particles are converted in a unidirectional manner outside the plasma compartment to medium (3 apoA-I molecules per particle) or large (4 apoA-I molecules per particle) HDL particles, which are subsequently removed from the circulation by the liver (Colvin et al. 1999. J. Lipid Res. 40: 1782;-1792; Huggins et al. 2000. J. Lipid Res. 41: 384;-394). The purpose of the present study was to determine whether the reduction in concentration of medium HDL in African green monkeys consuming n-3 polyunsaturated versus saturated fat diets resulted from decreased in vivo production or increased catabolism. Tracer small LpA-I (HDL containing only apoA-I) were isolated, without ultracentrifugation, by gel filtration and immunoaffinity chromatography and radiolabeled. After injection, the specific activity of apoA-I in small, medium, and large HDL was determined, and the kinetic data were analyzed using our previously published multicompartmental model for HDL subfraction metabolism. We found a significant reduction of apoA-I concentration in medium HDL in the animals fed n-3 polyunsaturated fat (31.2 +/- 0.7 mg/dl) compared with animals fed saturated fat (85.4 +/- 11.9 mg/dl; P = 0.002). The production rates of apoA-I in small, medium, and large HDL were similar in both diet groups; however, there was a significant increase in the fractional catabolic rate of apoA-I in medium HDL in the animals fed n-3 polyunsaturated fat (2.188 +/- 0.501 pools/day) compared with animals fed saturated fat (0.714 +/- 0.191 pools/day; P = 0.02). We conclude that n-3 polyunsaturated fat reduces HDL cholesterol concentration by increasing the fractional catabolic rate of medium-sized HDL particles in African green monkeys.
Huggins
K W
KW
Department of Pathology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.
Colvin
P L
PL
Burleson
E R
ER
Kelley
K
K
Sawyer
J K
JK
Barrett
P H
PH
Rudel
L L
LL
Parks
J S
JS
D000818:Animals; D016632:Apolipoprotein A-I / Q000032:analysis / Q000097:blood; D016633:Apolipoprotein A-II / Q000097:blood; D015153:Blotting, Western; D002522:Chlorocebus aethiops; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004041:Dietary Fats / Q000494:pharmacology; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008055:Lipids / Q000097:blood; D008075:Lipoproteins, HDL / Q000032:analysis / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D010316:Particle Size; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D007457:Iodine Radioisotopes; D008055:Lipids; D008075:Lipoproteins, HDL; D014280:Triglycerides; D002784:Cholesterol