HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix All Versions of this Article: dc07-0015v1 30/8/1945    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rosenson, R. S. Articles by Rademaker, A. W. Search for Related Content PubMed PubMed Citation Articles by Rosenson, R. S. Articles by Rademaker, A. W. Social Bookmarking                What's this?

Fenofibrate Therapy Ameliorates Fasting and Postprandial Lipoproteinemia, Oxidative Stress, and the Inflammatory Response in Subjects With Hypertriglyceridemia and the Metabolic Syndrome

¹ Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan
² Lipoprotein and Hemorheology Research Facility, Division of Cardiology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois
³ Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois

Address correspondence and reprint requests to Robert S. Rosenson, MD, Division of Cardiovascular Medicine, University of Michigan, Domino's Farms, 24 Frank Lloyd Wright Dr., Lobby A, Ann Arbor, MI 48106-0736. E-mail: rrosenso{at}umich.edu

OBJECTIVE—The aim of this study was to determine the effects of fenofibrate (160 mg/day) on fasting and postprandial lipoproteins, oxidized fatty acids, and inflammatory mediators in subjects with hypertriglyceridemia and the metabolic syndrome.

RESEARCH DESIGN AND METHODS—Fifty-nine subjects with fasting hypertriglyceridemia (1.7 and <6.9 mmol/l) and two or more of the Adult Treatment Panel III criteria for the metabolic syndrome were randomly assigned to fenofibrate (160 mg/day) or placebo in a double-blind, controlled clinical trial.

RESULTS—Fenofibrate treatment lowered fasting triglycerides (–46.1%, P < 0.0001) and postprandial (area under the curve) triglycerides (–45.4%, P < 0.0001) due to significant reductions in postprandial levels of large (–40.8%, P < 0.0001) and medium (–49.5%, P < 0.0001) VLDL particles. The number of fasting total LDL particles was reduced in fenofibrate-treated subjects (–19.0%, P = 0.0033) primarily due to reductions in small LDL particles (–40.3%, P < 0.0001); these treatment differences persisted postprandially. Fasting and postprandial oxidized fatty acids were reduced in fenofibrate-treated subjects compared with placebo-administered subjects (–15.3%, P = 0.0013, and 31.0%, P < 0.0001, respectively), and fenofibrate therapy lowered fasting and postprandial soluble vascular cell adhesion molecule-1 (VCAM-1) (–10.9%, P = 0.0005, and –12.0%, P = 0.0001, respectively) as well as fasting and postprandial soluble intercellular adhesion molecule-1 (ICAM-1) (–14.8%, P < 0.0001, and –15.3%, P < 0.0001, respectively). Reductions in VCAM-1 and ICAM-1 were correlated with reductions in fasting and postprandial large VLDL particles (P < 0.0001) as well as postprandial oxidized fatty acids (P < 0.0005).

CONCLUSIONS—Triglyceride-lowering therapy with fenofibrate reduced fasting and postprandial free fatty acid oxidation and inflammatory responses, and these antiatherosclerotic effects were most highly correlated with reductions in large VLDL particles.

Abbreviations: apoB, apolipoprotein B • AUC, area under the curve • CHD, coronary heart disease • ICAM-1, intercellular adhesion molecule-1 • IDL, intermediate-density lipoprotein • NF-B, nuclear factor- B • NMR, nuclear magnetic resonance • OH-FA, monohydroxy fatty acid • oxLDL, oxidized LDL • VA-HIT, Veterans Administration HDL Intervention Trial • VCAM-1, vascular cell adhesion molecule-1

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Macias-Gonzalez, F. Cardona, M. Queipo-Ortuno, R. Bernal, M. Martin, and F. J. Tinahones PPAR{gamma} mRNA Expression Is Reduced in Peripheral Blood Mononuclear Cells after Fat Overload in Patients with Metabolic Syndrome J. Nutr., May 1, 2008; 138(5): 903 - 907. [Abstract] [Full Text] [PDF]

				Y.-J. Chen and J. Quilley Fenofibrate Treatment of Diabetic Rats Reduces Nitrosative Stress, Renal Cyclooxygenase-2 Expression, and Enhanced Renal Prostaglandin Release J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 658 - 663. [Abstract] [Full Text] [PDF]