Hypocholesterolemic effect of lycopene and beta-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages.
Beta-Carotene and lycopene are derived from plants, and they share similar initial synthetic pathway with cholesterol, which is synthesized in animal but not in plant cells. Thus, we sought to analyze the effect of carotenoids on macrophage cholesterol metabolism, in comparison to the effect of LDL cholesterol and of the cholesterol synthesis inhibitor, fluvastatin. In J-774 A. 1 macrophage cell line, the cellular cholesterol synthesis from [3H]-acetate, but not from [14C] mevalonate, was suppressed by 63% any by 73% following cell incubation with beta-carotene or lycopene (10 microM) respectively, in comparison to a 90% and 91% inhibition by LDL (100 micrograms of cholesterol), or by fluvastatin (10 micrograms/ml) respectively. However, unlike LDL derived cholesterol, which also suppresses macrophage LDL receptor activity, lycopene and beta-carotene augmented the activity of the macrophage LDL receptor, similarly to the effect of fluvasfatin. In agreement with these in vitro observations, dietary supplementation of tomato's lycopene (60 mg/day) to 6 males for a 3 months period resulted in a significant 14% reduction in their plasma LDL cholesterol concentrations. We thus conclude that dietary supplementation of carotenoids may act as moderate hypocholesterolemic agents, secondary to their inhibitory effect on macrophage 3-hydroxy-3-methyl glutaryl coenzyme A (HMGCoA) reductase, the rate limiting enzyme in cholesterol synthesis.
Fuhrman
B
B
Lipid Research Laboratory, Technion Faculty of Medicine, Rappaport Family Institute for Research in the Medical Sciences, Haifa, Israel.
Elis
A
A
Aviram
M
M
D019342:Acetic Acid / Q000378:metabolism; D000328:Adult; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002338:Carotenoids / Q000494:pharmacology*; D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL / Q000097:blood; D000077276:Lycopene; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008798:Mevalonic Acid / Q000378:metabolism; D051379:Mice; D011973:Receptors, LDL / Q000187:drug effects* / Q000378:metabolism*; D019207:beta Carotene / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D019207:beta Carotene; D002338:Carotenoids; D002784:Cholesterol; D019342:Acetic Acid; D008798:Mevalonic Acid; D000077276:Lycopene