Gemfibrozil reduces non-high-density lipoprotein cholesterol in exogenously hypercholesterolemic (ExHC) rats fed a high-cholesterol diet.

Gemfibrozil is a widely used drug prescribed to elevate serum high-density lipoprotein (HDL) cholesterol levels and lower triacylglycerols. The present study was done to determine if the drug would alleviate hypercholesterolemia in exogenously hypercholesterolemic (ExHC) rats. In the drug-treated ExHC rats, the serum non-HDL cholesterol levels were lowered and the ratio of the non HDL cholesterol to serum triacylglycerols was decreased to the extent seen in the drug-treated SD rats. Liver cholesterol and triacylglycerols were lowered in the drug-treated rats. There was also an increase in fecal excretion of neutral sterols and bile acids, particularly chenodeoxycholic and beta-muricholic acids. The drug elevated cholesterol 7 alpha-hydroxylase activity and mRNA abundance and acyl-CoA cholesterol acyltransferase activity in the liver, but did not influence low-density lipoprotein receptor mRNA level in the liver. Thus, gemfibrozil is effective in alleviating hypercholesterolemia in exogenously hypercholesterolemic rats, by partitioning hepatic cholesterol into biliary excretion.