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Consumption of boiled coffee raises serum cholesterol levels in humans. The diterpenes cafestol and kahweol in boiled coffee have been found to be responsible for the increase. To investigate the biochemical background of this effect, we studied the effects of cafestol and a mixture of cafestol/kahweol/isokahweol (48:47:5 w/w) on bile acid synthesis and cholesterol 7α-hydroxylase and sterol 27-hydroxylase in cultured rat hepatocytes.Dose-dependent decreases of bile acid mass production and cholesterol 7α-hydroxylase and sterol 27-hydroxylase activity were found, showing a maximal reduction of −91%, −79%, and −49% respectively, at a concentration of 20 μg/mL cafestol. The decrease in 7α-hydroxylase and 27-hydroxylase activity paralleled well the suppression of the respective mRNAs, being −79% and −77%, and −49% and −46%, respectively, at 20 μg/mL cafestol. Run-on data showed a reduction in 7α-hydroxylase and 27-hydroxylase gene transcriptional activity after incubation with cafestol. The mixture of cafestol/kahweol/isokahweol was less potent in suppression of bile acid synthesis and cholesterol 7α-hydroxylase. Cafestol (20 μg/mL) had no effect on lithocholic acid 6β-hydroxylase mRNA, another enzyme involved in bile acid synthesis. LDL-receptor, HMG-CoA reductase, and HMG-CoA synthase mRNAs were significantly decreased by cafestol (−18%, −20%, and −43%, respectively). We conclude that cafestol suppresses bile acid synthesis by downregulation of cholesterol 7α-hydroxylase and of, to a lesser extent, sterol 27-hydroxylase in cultured rat hepatocytes, whereas kahweol and isokahweol are less active. We suggest that suppression of bile acid synthesis may provide an explanation for the cholesterol-raising effect of cafestol in humans.

arteriosclerosis, thrombosis, and vascular biology

Cafestol, the Cholesterol-Raising Factor in Boiled Coffee, Suppresses Bile Acid Synthesis by Downregulation of Cholesterol 7α-Hydroxylase and Sterol 27-Hydroxylase in Rat Hepatocytes