POSTPRANDIAL APOLIPOPROTEIN B100 AND B48 METABOLISM IN FAMILIAL COMBINED HYPERLIPIDEMIA 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 contain ing particles. We investigated if normalization of fasting plasma trig lycerides (TG) by hypolipidaemic treatment results in improved metabol ism of apo B48 and apo B100 in six male subjects with FCH and compared them to six normolipidaemic controls. The FCH patients were studied b efore (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 ape 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 m l(-1)) and remnant fractions (REM; d:1.006-1.019 g ml(-1)) of apo B we re 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 increa sed maximally at 4 h by 81% in TRP and by 137% in REM compared to base line. In treated FCH, the postprandial ape B48 pattern normalized in T RP 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 t reated FCH, postprandial apo B100 remained unchanged vs. baseline in T RP and in REM suggesting hypersecretion of VLDL. The elimination of B1 00--assessed as area under the curve-in TRP (325 +/- 36 au.h; mean +/- SEM) and REM fractions (33.2 +/- 3.1 au.h), improved significantly af ter treatment (21.0 +/- 2.8 and 20.4 +/- 3.3 au.h, respectively). The ape 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 sub jects with ape B100 hypersecretion and increased fasting plasma apo B4 8 levels, reduction of fasting plasma TG improved, but did not normali ze, TRP ape B48 and B100 metabolism. However, therapy normalized postp randial apo B100 remnant metabolism. Impaired postprandial apo B metab olism may be instrumental in the development of premature atherosclero sis in FCH subjects.