β-VLDL accumulation in familial dysbetalipoproteinemia is associated with increased exchange or diffusion of chylomicron lipids to apo B-100 containing triglyceride-rich lipoproteins Original Research Article

To gain more insight into the accumulation of β-very low density lipoprotein (β-VLDL) in familial dysbetalipoproteinemia (FD), we followed the courses of the levels of retinyl palmitate (rp), α-tocopherol (α-T) and apolipoprotein (apo) B-48 in various lipoprotein fractions for up to 48 h in eight patients with FD and six normolipidemic control subjects after an oral fat load (50 g fat/m2 containing 150 000 IU of rp and 5000 IU of α-T). α-T was added because of its rapid transfer to other lipoproteins. Fasting apo B-48 concentration in FD was normal to strongly elevated, dependent on the fasting lipid concentrations. 3 h after fat loading, total apo B-48 content did not abnormally increase; while the apo B-100 content in the triglyceride-rich lipoprotein fraction remained stable. The levels of both vitamins increased considerably, especially in the remnant fraction (Sf 15–100), which in due course exclusively contained apo B-100 in most hyperlipidemic patients. This, together with the observation that peaks for rp and α-T were observed 3–6 h later than for apo B-48 strongly suggests that both vitamins transfer or diffuse rapidly towards the apo B-100 containing VLDL. RP is thus more a marker for this process, which also comprises chylomicron lipids, than a specific marker for chylomicrons. This process, first described here, appears decisive in the pathogenesis of FD.