Postprandial apolipoprotein B100 and B48 metabolism in familial combined hyperlipidaemia before and after reduction of fasting plasma triglycerides.
Hepatic VLDL overproduction in familial combined hyperlipidaemia (FCH) may delay the clearance of atherogenic apolipoprotein (apo) B containing particles. We investigated if normalization of fasting plasma triglycerides (TG) by hypolipidaemic treatment results in improved metabolism of apo B48 and apo B100 in six male subjects with FCH and compared them to six normolipidaemic controls. The FCH patients were studied before (TG, 5.2 +/- 1.2 mmol l-1; mean +/- SEM) and after therapy (TG, 2.1 +/- 0.3 mmol l-1) with either simvastatin (n = 4) or combined therapy with gemfibrozil (n = 2). The postprandial changes of apo B100 and apo B48 were studied after a single oral fat meal (24 h; 50 gram fat m-2). Changes in triglyceride rich particles (TRP; d < 1.006 g ml-1) and remnant fractions (REM; d:1.006-1.019 g ml-1) of apo B were quantitated by scanning silverstained SDS-PAGE (4-15%). Apo B48 in fasting TRP in untreated and treated FCH was 15% and 14% of total apo B, and 6% in controls (P < 0.05). In controls, postprandial B48 increased maximally at 4 h by 81% in TRP and by 137% in REM compared to baseline. In treated FCH, the postprandial apo B48 pattern normalized in TRP compared to the untreated state. Postprandial apo B100 in controls decreased in TRP and REM by 33% and 18% (P < 0.05). In untreated and treated FCH, postprandial apo B100 remained unchanged vs. baseline in TRP and in REM suggesting hypersecretion of VLDL. The elimination of B100--assessed as area under the curve--in TRP (32.5 +/- 3.6 au.h; mean +/- SEM) and REM fractions (33.2 +/- 3.1 au.h), improved significantly after treatment (21.0 +/- 2.8 and 20.4 +/- 3.3 au.h, respectively). The apo B48 clearance in TRP fractions was improved after treatment (4.3 +/- 1.4 au.h vs. 2.9 +/- 1.2 au.h; P = 0.06), but not in REM fractions (2.8 +/- 1.0 au.h vs. 1.8 +/- 0.5 au.h; NS). In conclusion, in FCH subjects with apo B100 hypersecretion and increased fasting plasma apo B48 levels, reduction of fasting plasma TG improved, but did not normalize, TRP apo B48 and B100 metabolism. However, therapy normalized postprandial apo B100 remnant metabolism. Impaired postprandial apo B metabolism may be instrumental in the development of premature atherosclerosis in FCH subjects.
Department of Internal Medicine, University Hospital, Utrecht, The Netherlands.
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Castro Cabezas
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Erkelens
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Kock
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De Bruin
D000328:Adult; D000368:Aged; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000378:metabolism*; D002648:Child; D002784:Cholesterol / Q000097:blood; D004359:Drug Therapy, Combination; D005215:Fasting; D005260:Female; D015248:Gemfibrozil / Q000008:administration & dosage*; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008148:Lovastatin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin; D014280:Triglycerides / Q000097:blood*
D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D014280:Triglycerides; D002784:Cholesterol; D008148:Lovastatin; D019821:Simvastatin; D015248:Gemfibrozil