Apolipoproteins C-II and C-III metabolism in hypertriglyceridemic patients. Effect of a drastic triglyceride reduction by combined diet restriction and fenofibrate administration

Abstract

Four hypertriglyceridemic patients, who had received an equilibrated high calorie diet and no lipid lowering drug for 1 month, were injected intravenously with 125I-apo C-II and 131I-apo C-III labeled homologous lipoproteins. Plasma and urine radioactivity, lipid and apolipoprotein levels were followed at regular intervals for 15 days. At the end of this first kinetic study the patients were advised to adhere for 1 month to a more restricted diet, limited in fat, and were given additionally 300 mg fenofibrate daily. After this treatment, a new kinetic study involving intravenous injection (similar to the first one) was performed. The protocols of both studies were identical. Treatment (diet plus drug) (1) reduced total cholesterol by 26 +/- 8%, triglycerides by 56 +/- 15%, apo C-II by 36 +/- 14%, and apo C-III by 48 +/- 10%; (2) modified the distribution of radioactivity between lipoproteins proportionally to the change in their mass ratio (decrease in VLDL and increase in HDL); (3) changed the kinetics of both apoproteins by rising the fractional removal rate, shortening residence time and decreasing the synthesis rate of both apolipoproteins C-II and C-III. The treatment was, however, unable to reduce the synthesis rate of apo C-III to normal, suggesting a major role of the apoprotein overproduction in the triggering of hypertriglyceridemia.