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.
Watts
G F
GF
School of Medicine and Pharmacology, University of Western Australia, West Australian Institute for Medical Research, Royal Perth Hospital, Perth, W Australia. gfwatts@cyllene.uwa.edu.au
Chan
D C
DC
Barrett
P H R
PH
O'Neill
F H
FH
Thompson
G R
GR
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000378:metabolism*; D000069059:Atorvastatin; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000097:blood*; D015243:Cholesterol, VLDL / Q000097:blood; D004311:Double-Blind Method; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy*; D008875:Middle Aged; D010840:Phytosterols; D011758:Pyrroles / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D015243:Cholesterol, VLDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010840:Phytosterols; D011758:Pyrroles; C021273:campesterol; D002784:Cholesterol; D000069059:Atorvastatin