Abstract
Apolipoprotein (apo)A-IV is synthesized in the small intestine during fat absorption and is incorporated onto the surface of nascent chylomicrons. In circulation, apoA-IV is displaced from the chylomicron surface by high density lipoprotein-associated C and E apolipoproteins; this exchange is critical for activation of lipoprotein lipase and chylomicron remnant clearance. The variant allele A-IV-2 encodes a Q360H polymorphism that increases the lipid affinity of the apoA-IV-2 isoprotein. We hypothesized that this would impede the transfer of C and E apolipoproteins to chylomicrons, and thereby delay the clearance of postprandial triglyceride-rich lipoproteins. We therefore measured triglycerides in plasma, Sf > 400 chylomicrons, and very low density lipoproteins (VLDL) in 14 subjects heterozygous for the A-IV-2 allele (1/2) and 14 subjects homozygous for the common allele (1/1) who were fed a standard meal containing 50 gm fat per m2 body surface area. All subjects had the apoE-3/3 genotype. Postprandial triglyceride concentrations in the 1/2 subjects were significantly higher between 2–5 h in plasma, chylomicrons, and VLDL, and peaked at 3 h versus 2 h for the 1/1 subjects. The area under the triglyceride time curves was greater in the 1/2 subjects (plasma, P = 0.045; chylomicrons, P = 0.027; VLDL, P = 0.063). A posthoc analysis of the frequency of the apoA-IV T347S polymorphism suggested that it had an effect on triglyceride clearance antagonistic to that of the A-IV-2 allele. We conclude that individuals heterozygous for the A-IV-2 allele display delayed postprandial clearance of triglyceride-rich lipoproteins. —Hockey, K. J., R. A. Anderson, V. R. Cook, R. R. Hantgan, and R. B. Weinberg. Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance.
Highlights
ApolipoproteinA-IV is synthesized in the small intestine during fat absorption and is incorporated onto the surface of nascent chylomicrons
There was a significant allele ϫ time interaction on postprandial triglyceride levels: mean triglycerides in plasma, Sf Ͼ 400 chylomicrons, and very low density lipoproteins (VLDL) peaked at 3 h in the 1/2 subjects versus 2 h in the 1/1 sub
Allelic variations in the apoE gene have long been known for their potent effect on postprandial lipid metabolism [10, 17,18,19,20,21], but recently, genetic polymorphisms in the genes for lipoprotein lipase (11 – 13), apoB [14,15,16], and intestinal fatty acid binding protein 2 [51] have been found to affect the postprandial lipoprotein response
Summary
Apolipoprotein (apo)A-IV is synthesized in the small intestine during fat absorption and is incorporated onto the surface of nascent chylomicrons. ApoA-IV is displaced from the chylomicron surface by high density lipoprotein-associated C and E apolipoproteins; this exchange is critical for activation of lipoprotein lipase and chylomicron remnant clearance. The variant allele A-IV-2 encodes a Q360H polymorphism that increases the lipid affinity of the apoA-IV-2 isoprotein We hypothesized that this would impede the transfer of C and E apolipoproteins to chylomicrons, and thereby delay the clearance of postprandial triglyceride-rich lipoproteins. Dietary triglycerides are hydrolyzed in the lumen of the small intestine, absorbed by the intestinal enterocytes, reesterified, and secreted into the mesenteric lymph as chylomicrons Following their entry into circulation, chylomicrons acquire apolipoprotein (apo)C-II, the cofactor for lipoprotein lipase, and apoE, a ligand for hepatic chylomicron remnant uptake, which are transferred to their surface from high density lipoproteins (HDL).
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