Relationships between changes in plasma lipid transfer proteins and apolipoprotein B-100 kinetics during fenofibrate treatment in the metabolic syndrome.
The aim of the present study was to investigate the association between changes in apoB (apolipoprotein B-100) kinetics and plasma PLTP (phospholipid transfer protein) and CETP (cholesteryl ester transfer protein) activities in men with MetS (the metabolic syndrome) treated with fenofibrate. Eleven men with MetS underwent a double-blind cross-over treatment with fenofibrate (200 mg/day) or placebo for 5 weeks. Compared with placebo, fenofibrate significantly increased the FCRs (fractional catabolic rates) of apoB in VLDL (very-low-density lipoprotein), IDL (intermediate-density lipoprotein) and LDL (low-density lipoprotein) (all P<0.01), with no significant reduction (-8%; P=0.131) in VLDL-apoB PR (production rate), but an almost significant increase (+15%, P=0.061) in LDL-apoB PR. Fenofibrate significantly lowered plasma TG [triacylglycerol (triglyceride); P<0.001], the VLDL-TG/apoB ratio (P=0.003) and CETP activity (P=0.004), but increased plasma HDL (high-density lipoprotein)-cholesterol concentration (P<0.001) and PLTP activity (P=0.03). The increase in PLTP activity was positively associated with the increase in both LDL-apoB FCR (r=0.641, P=0.034) and PR (r=0.625, P=0.040), and this was independent of the fall in plasma CETP activity and lathosterol level. The decrease in CETP activity was positively associated with the decrease in VLDL-apoB PR (r=0.615, P=0.044), but this association was not robust and not independent of changes in PLTP activity and lathosterol levels. Hence, in MetS, the effects of fenofibrate on plasma lipid transfer protein activities, especially PLTP activity, may partially explain the associated changes in apoB kinetics.
Watts
Gerald F
GF
Lipoprotein Research Unit, School of Medicine and Pharmacology, University of Western Australia, Perth, WA 6000 Australia. gfwatts@cyllene.uwa.edu.au
Ji
Juying
J
Chan
Dick C
DC
Ooi
Esther M M
EM
Johnson
Anthony G
AG
Rye
Kerry-Anne
KA
Barrett
P Hugh R
PH
D000328:Adult; D053299:Apolipoprotein B-100 / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000188:drug therapy; D049294:Phospholipid Transfer Proteins / Q000097:blood*
D053299:Apolipoprotein B-100; D053480:Cholesterol Ester Transfer Proteins; D000960:Hypolipidemic Agents; D008055:Lipids; D008074:Lipoproteins; D049294:Phospholipid Transfer Proteins; C001521:lathosterol; D002784:Cholesterol; D011345:Fenofibrate