Delayed clearance of postprandial large TG-rich particles in normolipidemic carriers of LPL Asn291Ser gene variant.
The carrier frequency of Asn291Ser polymorphism of the lipoprotein lipase (LPL) gene is 4;-6% in the Western population. Heterozygotes are prone to fasting hypertriglyceridemia and low high density lipoprotein (HDL) cholesterol concentrations especially when secondary factors are superimposed on the genetic defect. We studied the LPL Asn291Ser gene variant as a modulator of postprandial lipemia in heterozygote carriers. Ten normolipidemic carriers were compared to ten control subjects, who were selected to have similar age, sex, BMI, and apolipoprotein (apo)E-phenotype. The subjects were given a lipid-rich mixed meal and their insulin sensitivity was determined by euglycemic hyperinsulinemic clamp technique. The two groups had comparable fasting triglycerides and glucose utilization rate during insulin infusion, but fasting HDL cholesterol was lower in carriers (1.25 +/- 0.05 mmol/L) than in the control subjects (1. 53 +/- 0.06 mmol/L, P = 0.005). In the postprandial state the most pronounced differences were found in the very low density lipoprotein 1 (VLDL1) fraction, where the carriers displayed higher responses of apoB-48 area under the curve (AUC), apoB-100 AUC, triglyceride AUC, and retinyl ester AUC than the control subjects. The most marked differences in apoB-48 and apoB-100 concentrations were observed late in the postprandial period (9 and 12 h), demonstrating delayed clearance of triglyceride-rich particles of both hepatic and intestinal origin. Postprandially, the carriers exhibited enrichment of triglycerides in HDL fraction. Thus, in normolipidemic carriers the LPL Asn291Ser gene variant delays postprandial triglyceride, apoB-48, apoB-100, and retinyl ester metabolism in VLDL1 fraction and alters postprandial HDL composition compared to matched non-carriers.
Mero
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Division of Endocrinology and Diabetes, Department of Medicine, University of Helsinki, Haartmaninkatu 4, P.O. Box 340, FIN-00029 HUCH, Helsinki, Finland.
Suurinkeroinen
L
L
Syvänne
M
M
Knudsen
P
P
Yki-Järvinen
H
H
Taskinen
M R
MR
D000328:Adult; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood; D001483:Base Sequence; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D017931:DNA Primers / Q000235:genetics; D004041:Dietary Fats / Q000008:administration & dosage; D005215:Fasting / Q000097:blood; D005260:Female; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D007333:Insulin Resistance; D008071:Lipoprotein Lipase / Q000235:genetics* / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D001786:Blood Glucose; D017931:DNA Primers; D004041:Dietary Fats; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol; D008071:Lipoprotein Lipase