The coffee diterpene cafestol increases plasma triacylglycerol by increasing the production rate of large VLDL apolipoprotein B in healthy normolipidemic subjects

Background: Cafestol is a diterpene in unfiltered coffee that raises plasma triacylglycerol in humans. Objective: We studied whether cafestol increases plasma triacylglycerol by increasing the production rate or by decreasing the fractional catabolic rate of VLDL1 [Svedberg flotation unit (Sf) 60-400] apolipoprotein (apo) B. In addition, we studied the effect of cafestol on the composition of VLDL1 and VLDL2 (Sf 2060). Design: Eight healthy normolipidemic men were administered a daily dose of 75 mg cafestol for 2 wk. A bolus injection of 7 mg L-[5,5,5-2H3]leucine/kg body wt was given after a baseline period with no cafestol and again after treatment with cafestol. We derived kinetic constants to describe the metabolism of VLDL1 apo B by using a multicompartmental model. Results: Cafestol significantly increased plasma triacylglycerol by 31␘r 0.32 mmol/L (95␌I: 0.03, 0.61); the increase was due mainly to a nonsignificant rise in VLDL1 triacylglycerol of 57␘r 0.23 mmol/L (95␌I: -0.02, 0.48). Cafestol significantly increased the mean rate of VLDL1 apo B production by 80␘r 755 mg/d (95␌I: 0.2, 5353), whereas it did not significantly change the mean fractional catabolic rate of VLDL1 apo B (mean increase of 3 pools/d; 95␌I: -4, 10]). Cafestol did not change the composition of VLDL1. A significant increase in the ratio of VLDL2 cholesteryl ester to triacylglycerol indicates that VLDL2 became enriched with cholesteryl esters at the cost of triacylglycerol. Conclusion: Cafestol increases plasma triacylglycerol by increasing the production rate of VLDL1 apo B, probably via increased assembly of VLDL1 in the live