Inhibition of lipid synthesis and secretion in long-term cultures of adult rat hepatocytes by alpha-asarone.
In this work we studied the effect of alpha-asarone, a hypolipidemic active principle of Guatteria gaumeri Greenman, on hepatic lipid metabolism using adult rat hepatocytes cultured on a feeder layer of 3T3 cells. These cultures synthesize and secrete for at least two weeks various lipids from [14C]-acetic and [14C]-oleic acid. Exposure for one or two weeks to 10 micrograms/ml of alpha-asarone decreased the secretion of various lipids to the culture medium; triacylglycerol secretion was inhibited by 80-97%, phospholipid secretion by 70-87%, cholesterol by 64-70%, and cholesterol esters by 50-92%. The incorporation of [14C]-acetic acid into cellular lipids decreased by 30-81% and that of [14C]-oleic acid into phospholipids by 25-47% whereas the incorporation of [14C]-oleic acid into triglycerides and cholesterol esters increased 3.2 fold and by 28-36%, respectively. Similarly, the activities of glycerol-3-phosphate dehydrogenase and malic enzyme, marker enzymes of glycerolipid and fatty acid synthesis, decreased by 22-50% and 30-76%, respectively. Our results show that the exposure of the 3T3-hepatocyte cultures to micromolar concentrations of alpha-asarone significantly inhibits lipid secretion and probably lipid synthesis. They also suggest that at least part of the hypolipidemic effect could be due to a decrease in the secretion of lipids (i.e., lipoproteins) by the hepatocytes.
Hernández
A
A
Pharmacology and Toxicology Department, Centro de Investigación y Estudios Avanzados del IPN, México D.F.
López
M L
ML
Chamorro
G
G
Mendoza-Figueroa
T
T
D016475:3T3 Cells; D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D002478:Cells, Cultured; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D010946:Plants, Medicinal; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D000081248:Allylbenzene Derivatives; D000840:Anisoles; D008055:Lipids; D009829:Oleic Acids; C012195:asarone; D019301:Oleic Acid; D019342:Acetic Acid