Effect of a statin on hepatic apolipoprotein B-100 secretion and plasma campesterol levels in the metabolic syndrome

OBJECTIVE: We aimed to study the effect of atorvastatin, a statin, on cholesterol synthesis and absorption and VLDL-apoB metabolism in obese men with the metabolic syndrome.METHODS: A total of 25 dyslipidaemic obese men were randomized to atorvastatin (n = 13) ( 40 mg/day) or matching placebo ( n = 12) for 6 weeks. Hepatic secretion and fractional catabolic rate (FCR) of VLDL-apoB was measured using an intravenous bolus of d(3)-leucine before and after treatment. ApoB isotopic enrichment was measured using GCMS and multicompartmental modelling. Plasma lathosterol: cholesterol and campesterol: cholesterol ratios were determined to assess cholesterol synthesis and cholesterol absorption, respectively.RESULTS: Compared with placebo, atorvastatin significantly decreased (P<0.05) total cholesterol, triglyceride, LDL-cholesterol and VLDL-apoB. Plasma lathosterol: cholesterol ratio decreased from 26.4 +/- 2.4 to 8.8 +/- 0.8, while the campesterol: cholesterol ratio increased from 26.5 +/- 4.4 to 38.6 +/- 5.8 (P<0.01). Atorvastatin also increased VLDL-apoB FCR from 3.82 +/- 0.33 to 6.30 +/- 0.75 pools/ day (P<0.01), but did not significantly alter VLDL-apoB secretion ( 12.8 +/- 1.7 to 13.8 +/- 2.0 mg/kg/day).CONCLUSIONS: In obesity, atorvastatin inhibits cholesterogenesis but increases intestinal cholesterol absorption. The increased cholesterol absorption may counteract the inhibitory effect on hepatic VLDL- apoB secretion, but it does not apparently influence enhanced catabolism of VLDL-apoB.