Hypocholesterolaemic effect of beta beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) in the male hamster.
Treatment of cholesterol-fed male hamsters kept on a diet of purina chow with beta beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a progressive hypocholesterolaemic effect, amounting to a 50% decrease in the cholesterol content of all plasma lipoproteins. The decrease in plasma cholesterol could be accounted for by activation of plasma-cholesterol efflux through the liver into the bile mediated by MEDICA 16-induced (a) increase of the number of liver LDL receptors, (b) activation of liver neutral cholesteryl ester hydrolase with a concomitant inhibition of liver acyl-CoA cholesterol acyltransferase, resulting in shifting of the liver cholesteryl ester/free-cholesterol cycle in the direction of free cholesterol, and (c) activation of cholesterol efflux from the liver into the bile. The increase in bile cholesterol output was accompanied by an increase in bile phospholipids but not in bile acids. In contrast with rats, MEDICA 16-treatment of male hamsters did not result in a hypotriacylglycerolaemic effect, inhibition of lipogenesis, nor in a substantial decrease in plasma apolipoprotein C-III content.
Mayorek
N
N
Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Bar-Tana
J
J
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001053:Apolipoproteins / Q000097:blood; D001646:Bile / Q000737:chemistry / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000172:deficiency*; D002791:Cholesterol, Dietary / Q000378:metabolism; D006224:Cricetinae; D004789:Enzyme Activation; D005069:Evaluation Studies as Topic; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000201:enzymology; D008297:Male; D008647:Mesocricetus; D010169:Palmitic Acids / Q000494:pharmacology*; D011973:Receptors, LDL / Q000032:analysis; D002787:Sterol Esterase / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism
D000924:Anticholesteremic Agents; D001053:Apolipoproteins; D002791:Cholesterol, Dietary; D008074:Lipoproteins; D010169:Palmitic Acids; D011973:Receptors, LDL; C056166:MEDICA 16; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase