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.
Nagao
K
K
Department of Food Science and Technology, Faculty of Agriculture, Kyushu University, Fukuoka, Japan.
Yoshida
S
S
Nakagiri
H
H
Sakono
M
M
Sato
M
M
Imaizumi
K
K
D000818:Animals; D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000097:blood*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005243:Feces / Q000737:chemistry; D005260:Female; D015248:Gemfibrozil / Q000627:therapeutic use*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism; D006937:Hypercholesterolemia / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D002785:Sterol O-Acyltransferase / Q000235:genetics / Q000378:metabolism
D001053:Apolipoproteins; D002791:Cholesterol, Dietary; D000960:Hypolipidemic Agents; D012333:RNA, Messenger; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; D002785:Sterol O-Acyltransferase; D015248:Gemfibrozil