Effect of lovastatin on the secretion of very low density lipoprotein lipids and apolipoprotein B in the hypertriglyceridemic Zucker obese rat.
Recent studies demonstrated that inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase lower plasma triglyceride primarily by decreasing hepatic secretion of very low density lipoproteins (VLDL). A possible mechanism is that inhibition of cholesterol synthesis interferes with the assembly of VLDL particles. Since one molecule of apolipoprotein (apo) B is required for the proper assembly and secretion of each VLDL and secretion of apo B may be regulated by various lipid components of the lipoproteins, question arises whether HMG-CoA reductase inhibitors also decrease the secretion of apo B. To address this issue, we investigated the effect of lovastatin on the secretion rate of VLDL-apo B and on the composition of VLDL in the Zucker obese rat; a model for genetic hypertriglyceridemia. Lovastatin treatment (4 mg/kg day x 13 days), as compared with placebo, decreased the concentrations of fasting plasma triglyceride (1740 +/- 170 vs. 3130 +/- 790 micrograms/ml) and VLDL-triglyceride (1379 +/- 59 vs. 3082 +/- 715 micrograms/ml). There was a small but non-significant decrease in VLDL-apo B (19 +/- 2 micrograms/ml vs. 26 +/- 7 micrograms/ml). Thus, lovastatin significantly decreased the ratio of triglyceride to apo B in VLDL (76 in lovastatin vs. 124 in placebo group). Secretion rates of VLDL-lipids and VLDL-apo B were measured after intravenous injection of Triton WR-1339.(ABSTRACT TRUNCATED AT 250 WORDS)
Kasim
S E
SE
Department of Medicine, Veterans Administration Medical Center, Allen Park, MI.
Elovson
J
J
Khilnani
S
S
Almario
R U
RU
Jen
K L
KL
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015228:Hypertriglyceridemia / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000737:chemistry; D008148:Lovastatin / Q000494:pharmacology*; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011924:Rats, Zucker; D014280:Triglycerides / Q000097:blood
D001055:Apolipoproteins B; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D011092:Polyethylene Glycols; D002784:Cholesterol; D008148:Lovastatin; C016811:tyloxapol