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Mechanism of action of a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor on apolipoprotein B-100 kinetics in visceral obesity.
J Clin Endocrinol Metab. 2002 May; 87(5):2283-9.JC

Abstract

We examined the effect of atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the kinetics of apolipoprotein B-100 (apoB) metabolism in 25 viscerally obese men in a placebo-controlled study. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) apoB kinetics were measured using an iv bolus injection of [(2)H(3)]leucine. ApoB isotopic enrichment was measured using gas chromatography-mass spectrometry. Kinetic parameters were derived by using a multicompartmental model (SAAM-II). Compared with the placebo group, atorvastatin treatment resulted in significant (P < 0.001) decreases in total cholesterol (-34%), triglyceride (-19%), LDL cholesterol (-42%), total apoB (-39%), and lathosterol (-86%); VLDL-apoB, IDL-apoB, and LDL-apoB pool sizes also fell significantly (P < 0.002) by -27%, -22%, and -41%, respectively. This was associated with an increase in the fractional catabolic rates of VLDL-apoB (+58%, P = 0.019), IDL-apoB (+40%, P = 0.049), and LDL-apoB (+111%, P = 0.001). However, atorvastatin did not significantly alter the production and conversion rates of apoB in all lipoproteins. We conclude that in obese subjects, atorvastatin decreases the plasma concentration of all apoB-containing lipoproteins chiefly by increasing their catabolism and not by decreasing their production or secretion. This may be owing to up-regulation of hepatic receptors as a consequence of inhibition of cholesterogenesis.

Authors+Show Affiliations

Department of Medicine, University of Western Australia, Western Australian Institute for Medical Research, Royal Perth Hospital, Perth, Western Australia 6847.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11994377

Citation

Chan, Dick C., et al. "Mechanism of Action of a 3-hydroxy-3-methylglutaryl Coenzyme a Reductase Inhibitor On Apolipoprotein B-100 Kinetics in Visceral Obesity." The Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 5, 2002, pp. 2283-9.
Chan DC, Watts GF, Barrett PH, et al. Mechanism of action of a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor on apolipoprotein B-100 kinetics in visceral obesity. J Clin Endocrinol Metab. 2002;87(5):2283-9.
Chan, D. C., Watts, G. F., Barrett, P. H., Mori, T. A., Beilin, L. J., & Redgrave, T. G. (2002). Mechanism of action of a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor on apolipoprotein B-100 kinetics in visceral obesity. The Journal of Clinical Endocrinology and Metabolism, 87(5), 2283-9.
Chan DC, et al. Mechanism of Action of a 3-hydroxy-3-methylglutaryl Coenzyme a Reductase Inhibitor On Apolipoprotein B-100 Kinetics in Visceral Obesity. J Clin Endocrinol Metab. 2002;87(5):2283-9. PubMed PMID: 11994377.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanism of action of a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor on apolipoprotein B-100 kinetics in visceral obesity. AU - Chan,Dick C, AU - Watts,Gerald F, AU - Barrett,P Hugh R, AU - Mori,Trevor A, AU - Beilin,Lawrence J, AU - Redgrave,Trevor G, PY - 2002/5/8/pubmed PY - 2002/6/18/medline PY - 2002/5/8/entrez SP - 2283 EP - 9 JF - The Journal of clinical endocrinology and metabolism JO - J Clin Endocrinol Metab VL - 87 IS - 5 N2 - We examined the effect of atorvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the kinetics of apolipoprotein B-100 (apoB) metabolism in 25 viscerally obese men in a placebo-controlled study. Very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) apoB kinetics were measured using an iv bolus injection of [(2)H(3)]leucine. ApoB isotopic enrichment was measured using gas chromatography-mass spectrometry. Kinetic parameters were derived by using a multicompartmental model (SAAM-II). Compared with the placebo group, atorvastatin treatment resulted in significant (P < 0.001) decreases in total cholesterol (-34%), triglyceride (-19%), LDL cholesterol (-42%), total apoB (-39%), and lathosterol (-86%); VLDL-apoB, IDL-apoB, and LDL-apoB pool sizes also fell significantly (P < 0.002) by -27%, -22%, and -41%, respectively. This was associated with an increase in the fractional catabolic rates of VLDL-apoB (+58%, P = 0.019), IDL-apoB (+40%, P = 0.049), and LDL-apoB (+111%, P = 0.001). However, atorvastatin did not significantly alter the production and conversion rates of apoB in all lipoproteins. We conclude that in obese subjects, atorvastatin decreases the plasma concentration of all apoB-containing lipoproteins chiefly by increasing their catabolism and not by decreasing their production or secretion. This may be owing to up-regulation of hepatic receptors as a consequence of inhibition of cholesterogenesis. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/11994377/Mechanism_of_action_of_a_3_hydroxy_3_methylglutaryl_coenzyme_a_reductase_inhibitor_on_apolipoprotein_B_100_kinetics_in_visceral_obesity_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.87.5.8455 DB - PRIME DP - Unbound Medicine ER -