| Mechanism of Action of a Peroxisome Proliferator-Activated Receptor (PPAR)-{delta} Agonist on Lipoprotein Metabolism in Dyslipidemic Subjects with Central Obesity. | |
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MedLine Citation:
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PMID: 21816786 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Context: Dyslipidemia increases the risk of cardiovascular disease in obesity. Peroxisome proliferator-activated receptor (PPAR)-δ agonists decrease plasma triglycerides and increase high-density lipoprotein (HDL)-cholesterol in humans. Objective: The aim of the study was to examine the effect of GW501516, a PPAR-δ agonist, on lipoprotein metabolism. Design, Setting, and Intervention: We conducted a randomized, double-blind, crossover trial of 6-wk intervention periods with placebo or GW501516 (2.5 mg/d), with 2-wk placebo washout between treatment periods. Participants: We recruited 13 dyslipidemic men with central obesity from the general community. Main Outcome Measures: We measured the kinetics of very low-density lipoprotein (VLDL)-, intermediate-density lipoprotein-, and low-density lipoprotein (LDL)-apolipoprotein (apo) B-100, plasma apoC-III, and high-density lipoprotein (HDL) particles (LpA-I and LpA-I:A-II). Results: GW501516 decreased plasma triglycerides, fatty acid, apoB-100, and apoB-48 concentrations. GW501516 decreased the concentrations of VLDL-apoB by increasing its fractional catabolism and of apoC-III by decreasing its production rate (P < 0.05). GW501516 reduced VLDL-to-LDL conversion and LDL-apoB production. GW501516 increased HDL-cholesterol, apoA-II, and LpA-I:A-II concentrations by increasing apoA-II and LpA-I:A-II production (P < 0.05). GW501516 decreased cholesteryl ester transfer protein activity, and this was paralleled by falls in the triglyceride content of VLDL, LDL, and HDL and the cholesterol content of VLDL and LDL. Conclusions: GW501516 increased the hepatic removal of VLDL particles, which might have resulted from decreased apoC-III concentration. GW501516 increased apoA-II production, resulting in an increased concentration of LpA-I:A-II particles. This study elucidates the mechanism of action of this PPAR-δ agonist on lipoprotein metabolism and supports its potential use in treating dyslipidemia in obesity. |
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Authors:
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Esther M M Ooi; Gerald F Watts; Dennis L Sprecher; Dick C Chan; P Hugh R Barrett |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-3 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: - ISSN: 1945-7197 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Metabolic Research Centre (E.M.M.O., G.F.W., D.C.C., P.H.R.B.), School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6847, Australia; Lipid Metabolism Laboratory (E.M.M.O.), Jean Mayer U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, and the Friedman School of Nutrition Science and Policy at Tufts University and Tufts University School of Medicine, Boston, Massachusetts 02111; and Discovery Medicine (D.L.S.), Cardiovascular-Urology Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, Pennsylvania 19406. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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