Effect of atorvastatin on chylomicron remnant metabolism in visceral obesity: a study employing a new stable isotope breath test.
Elevated plasma concentration of chylomicron remnants may be causally related to atherosclerosis in obesity. We examined the effect of atorvastatin on chylomicron remnant metabolism in 25 obese men with dyslipidaemia. A remnant-like emulsion labeled with cholesteryl [(13)C]oleate was injected intravenously into patients; the fractional catabolic rate (FCR) of the remnant-like emulsion was determined by measurement of (13)CO(2) in the breath and analyzed using compartmental modelling. Compared with placebo, atorvastatin significantly decreased the plasma concentrations of total cholesterol, triglycerides, LDL cholesterol, apolipoprotein B (apoB), and lathosterol (P < 0.001). ApoB-48 and remnant-like particle-cholesterol (RLP-C) both decreased significantly by 23% (P = 0.002) and 33% (P = 0.045), respectively. The FCR of the remnant-like emulsion increased significantly from 0.054 +/- 0.008 to 0.090 +/- 0.010 pools/h (P = 0.002). The decrease in RLP-C was associated with the decrease in plasma triglycerides (r = 0.750, P = 0.003). Furthermore, the change in FCR of remnant-like emulsions was inversely associated with the change in LDL-C (r = -0.575, P = 0.040), suggesting removal of LDL and chylomicron remnants by similar hepatic receptor pathways. We conclude that in obese subjects, inhibition of cholesterol synthesis with atorvastatin decreases the plasma concentrations of both LDL-C and triglyceride-rich remnants and that this may be partially due to an enhancement in hepatic clearance of these lipoproteins.
Chan
Dick C
DC
University Department of Medicine, Royal Perth Hospital, GPO Box X2213, Perth, Western Australia 6847, Australia.
Watts
Gerald F
GF
Barrett
P Hugh R
PH
Martins
Ian J
IJ
James
Anthony P
AP
Mamo
John C L
JC
Mori
Trevor A
TA
Redgrave
Trevor G
TG
D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D015992:Body Mass Index; D001944:Breath Tests; D002245:Carbon Dioxide / Q000032:analysis*; D002247:Carbon Isotopes; D002784:Cholesterol / Q000097:blood; D053298:Chylomicron Remnants; D002914:Chylomicrons / Q000097:blood* / Q000187:drug effects; D004311:Double-Blind Method; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism; D009765:Obesity / Q000097:blood* / Q000188:drug therapy; D010919:Placebos; D011758:Pyrroles / Q000627:therapeutic use*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood; D014781:Viscera
D000924:Anticholesteremic Agents; D002247:Carbon Isotopes; D053298:Chylomicron Remnants; D002914:Chylomicrons; D006538:Heptanoic Acids; D008074:Lipoproteins; D010919:Placebos; D011758:Pyrroles; D014280:Triglycerides; D002245:Carbon Dioxide; D002784:Cholesterol; D000069059:Atorvastatin