Chylomicron processing in familial dysbetalipoproteinemia and familial combined hyperlipidemia studied with vitamin A and E as markers: a new physiological concept

In previous work we identified a transfer/diffusion process occurring in th e postprandial state that more or less contributes to the accumulation of b eta-VLDL in familial dysbetalipoproteinemia (FD). Here we present a new the oretical concept underlying chylomicron processing developed on the basis o f extended quantitative analyses of fat loading experiments, with both vita mins A and E, performed in patients with familial combined hyperlipidemia ( FCH) in comparison to patients with FD and control subjects. Recovery of tr iglycerides from the fat load in the plasma triglyceride pool was < 4%, ind icating a very effective lipolysis process with an active remnant generatio n. Vitamin A from the fat load was, over 48 h, quantitatively recovered in the plasma lipoprotein pool; vitamin E was recovered to 22-41%. Nevertheles s, transfer/diffusion of both vitamins showed similar patterns. At equilibr ium, their contents correlated strongly with the lipoprotein concentrations , the slopes being similar for control subjects and both groups of patients . Only in those FD patients with the highest lipid values, did the vitamin A/lipoprotein mass ratio in the Sf > 100 fraction deviate from the total gr oup mean. In the Sf 15-100 fraction, most specific for 'remnants', vitamin A/cholesterol ratios for all subjects were uniform proving that beta-VLDL f ormation is a thermodynamic process regulated by concentration gradients an d the lipophilicity of lipoprotein constituents, not a typical feature for patients with FD. In patients with FD, vitamin A in the plasma pool was rec overed excessively (276%) in line with recognition in Various pools as a re sult of the transfer/diffusion process in plasma. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.