Research Department Pharmaceuticals Division, Sumitomo Chemical Company, Ltd., Osaka (Japan)
Summary
(1)The effect of dl-N-(α-methylbenzyl) linoleamide (MBLA) and its optically active isomers (d-MBLA and l-MBLA) on cholesterol metabolism was studied in rats. After administering MBLA, d-MBLA and l-BMLA with [4-14C]cholesterol, total [4-14C]cholesterol levels in the plasma and liver, and its ester ratio in the liver were markedly depressed after 4 h. After 8 h, the same results were obtained, and the esterified [4-14C]cholesterol ratio in the small intestine was also depressed, but there was no significant difference after 24 h. The inhibitory effect on plasma and liver [4-14C]cholesterol pools was in the order d-MBLA > MBLA > l-MBLA.
(2)The cholesterol-lowering effect of MBLA was not decreased after administering it for 4 weeks.
(3)After administering MBLA, d-MBLA and l-MBLA with [3H] cholesterol to thoracic-duct fistula rats, total [3H]cholesterol levels and its ester ratio in lymph were markedly depressed for 24 h. These results suggest that the cholesterol-lowering mechanism of these compounds is due to reduced cholesterol absorption from the intestines.
(4)Hepatic cholesterogenesis was accelerated when a diet containing 0.1 % of MBLA was administered for 1–2 weeks. The acceleration of cholesterol biosynthesis by inhibitors of cholesterol absorption is considered to be due to a homeostatic mechanism that maintains body cholesterol via a feedback control.
Key words: Cholesterogenesis, Cholesterol metabolism, Esterified cholesterol, Fatty acid amides, Lymph cholesterol, Optical isomerism, Thoracic-duct fistula
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