Alterations in rat serum lipids and apolipoproteins following clofibrate treatment

The in vivo effects of the hypolipidemic drug clofibrate (0.5 mmol/kg body wt daily p.o. for 7 days) on serum lipids and apolipoproteins have been studied in male rats. Clofibrate caused an increase in liver weight without affecting body weight. Triglyceride, total and free cholesterol and HDL cholesterol were decreased in sera of clofibrate-treated rats. The relative abundance, and accordingly the absolute quantities, of the polyunsaturated fatty acids linoleic (18:2), linolenic (18:3) and docosahexenoic (22:6) in serum triglyceride decreased in response to clofibrate treatment. The concentrations of serum apolipoproteins A-I, B and C-III were reduced in clofibrate-treated rats. The apolipoprotein E level was not altered. The distribution of apolipoproteins A-I, B, C-III and E between heparin-Mn supernatant and precipitate were unaffected. The unchanged C-III distribution indicates unaltered intravascular VLDL catabolism. Concurrent reductions in serum HDL cholesterol and ApoA-I in clofibrate-treated rats suggest a diminished production of lipoprotein particles containing ApoA-I. Reductions in serum ApoB and in the mass ratio of serum triglyceride to ApoB indicate a decrease in the number and size, respectively, of circulating triglyceride-rich lipoprotein particles. These observations suggest that the hypolipidemic effect of clofibrate in the normolipemic rat is caused mainly by diminished hepatic secretion, rather than by enhanced catabolism, of triglyceride-rich lipoproteins.