Abstract
Consumption of boiled coffee promotes an elevation of plasma cholesterol concentration in humans. The active compounds found in the lipid fraction of the coffee have been identified as the diterpenes cafestol and kahweol. We have studied the effects of pure cafestol on cholesterol metabolism in human skin fibroblasts (HSF). The uptake of [125I]-labeled tyramine cellobiose-labeled low density lipoprotein ([125I]TC-LDL) was decreased by about 50% (P < 0.05) after 18 h preincubation time with cafestol (20 μg/ml), as compared to the control cells. The specific binding of radiolabeled LDL was reduced by 54% (P < 0.05) after preincubation for 18 h with cafestol. A reduced amount of LDL receptors was demonstrated by a protein-normalized Scatchard plot analysis (20% decrease in Bmax) as well as by immunoblotting (25%) after cafestol incubation. No significant effect was observed on the level of mRNA for the LDL receptor after 11 and 23 h incubation with cafestol. Furthermore, we transfected HSF cells with a promoter region for the LDL receptor gene linked to a reporter gene, chloramphenicol acetyl transferase (CAT). No change was seen in the CAT activity after incubation with cafestol (20 μg/ml). Moreover, cafestol caused a 2.3-fold (P < 0.05) higher incorporation of radiolabeled [14C]oleic acid into cholesteryl esters after 24 h incubation, as compared to control cells, suggesting an increased acyl-CoA:cholesterol acyl transferase (ACAT) activity. Incorporation of [14C]acetate into cholesterol was reduced by approximately 40% (P < 0.05) with cafestol (20 μg/ml), as compared to control after 24 h preincubation, indicating a decreased 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity. Our results suggest that intake of cafestol may cause increased concentration of plasma cholesterol via the down-regulation of low density lipoprotein receptors by post-transcriptional mechanisms.—Halvorsen, B., T. Ranheim, M. S. Nenseter, A. C. Huggett, and C. A. Drevon. Effect of a coffee lipid (cafestol) on cholesterol metabolism in human skin fibroblasts. J. Lipid Res. 1998. 39: 901–912.
Highlights
Consumption of boiled coffee promotes an elevation of plasma cholesterol concentration in humans
When the cells are depleted of cholesterol, the LDL receptor gene is transcribed actively, and LDL is cleared from plasma and Abbreviations: acyl-CoA:cholesterol acyl transferase (ACAT), acyl-CoA:cholesterol acyltransferase; BSA, bovine serum albumin; CAT, chloramphenicol acetyl transferase; DMEM, Dulbecco’s modified Eagle’s medium; FCS, fetal calf serum; hydroxy-3-methylglutaryl CoA (HMG-CoA), 3-hydroxy-3-methylglutaryl coenzyme A; HSF, human skin fibroblasts; G3PDH, glyceraldehyde 3-phosphate dehydrogenase; LDL, low density lipoprotein; LPDS, lipoprotein-deficient serum; [125I]TC-LDL, 125I-labeled tyramine cellobiose-labeled LDL; PBS, phosphate-buffered saline; SRE-1, sterol regulatory element-1; SDS, sodium dodecyl sulfate; SSC, sodium chloride/sodium citrate; SREBP-1, sterol regulatory element binding protein-1
Our results demonstrate that the coffee lipid, cafestol, significantly reduced the binding, uptake, and degradation of radiolabeled LDL in human fibroblasts
Summary
Consumption of boiled coffee promotes an elevation of plasma cholesterol concentration in humans. Effect of a coffee lipid (cafestol) on cholesterol metabolism in human skin fibroblasts. When the cells are depleted of cholesterol, the LDL receptor gene is transcribed actively, and LDL is cleared from plasma and Abbreviations: ACAT, acyl-CoA:cholesterol acyltransferase; BSA, bovine serum albumin; CAT, chloramphenicol acetyl transferase; DMEM, Dulbecco’s modified Eagle’s medium; FCS, fetal calf serum; HMG-CoA, 3-hydroxy-3-methylglutaryl coenzyme A; HSF, human skin fibroblasts; G3PDH, glyceraldehyde 3-phosphate dehydrogenase; LDL, low density lipoprotein; LPDS, lipoprotein-deficient serum; [125I]TC-LDL, 125I-labeled tyramine cellobiose-labeled LDL; PBS, phosphate-buffered saline; SRE-1, sterol regulatory element-1; SDS, sodium dodecyl sulfate; SSC, sodium chloride/sodium citrate; SREBP-1, sterol regulatory element binding protein-1. The aim of this study was to examine the effect of the purified coffee-diterpene cafestol on cholesterol metabolism in human skin fibroblasts (HSF) and to explore the possible mechanism behind the plasma cholesterol-raising effect observed in humans
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