Postprandial changes of apoB-100 and apoB-48 in TG rich lipoproteins in familial combined hyperlipidemia.
Impaired chylomicron (chylo) remnant clearance and small VLDL overproduction are major metabolic abnormalities in familial combined hyperlipidemia (FCHL). Quantitative data on postprandial apolipoprotein B-48 (apoB-48) and apolipoprotein B-100 (apoB-100) in TG rich lipoproteins (TRL) in FCHL have not been reported before. Eight untreated FCHL patients and 10 matched controls underwent a 24 h oral fat load. Fasting apoB-48 and apoB-100 were significantly higher in all TRL in FCHL. Maximal concentrations of chylo-[Svedberg's flotation rate (Sf) >400] apoB-48 and apoB-100 were reached later in FCHL (at t = 6 h), in contrast to controls (t = 4 h). Maximal VLDL1-(Sf60-400)-apoB-48 occurred at the same time point (t = 2 h) in both, whereas VLDL1-apoB-100 was maximal at t = 4 h in both, most likely representing delayed VLDL clearance by preferential clearance of chylo and their remnants by competition for the same clearance mechanisms. VLDL2-(Sf20-60)-apoB-48 and VLDL2- apoB-100 decreased in FCHL, in contrast to an increase of apoB-48, and no change of apoB-100 in controls, suggesting impaired conversion of VLDL1-apoB-48 into VLDL2-apoB-48 in FCHL, and partly also of VLDL1-apoB-100. In conclusion, in FCHL clearance of large postprandial Sf >400 apoB-48 and apoB-100 TRL is delayed. ApoB-100 accumulates in the VLDL1 range postprandially in both FCHL and controls, reaching higher levels in FCHL and thereby conferring a higher atherogenic burden in the postprandial situation in FCHL.
Verseyden
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Department of Vascular Medicine F02.126, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, The Netherlands.
Meijssen
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Castro Cabezas
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D000328:Adult; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D002914:Chylomicrons / Q000737:chemistry / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism*; D004224:Diterpenes; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate / Q000502:physiology; D008875:Middle Aged; D019518:Postprandial Period / Q000502:physiology*; D000084562:Retinyl Esters; D014280:Triglycerides / Q000097:blood; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000097:blood
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D002914:Chylomicrons; D004041:Dietary Fats; D004224:Diterpenes; D008079:Lipoproteins, VLDL; D000084562:Retinyl Esters; D014280:Triglycerides; D014801:Vitamin A; C014794:retinol palmitate; C042067:retinol oleate; D002784:Cholesterol