Fenofibrate therapy ameliorates fasting and postprandial lipoproteinemia, oxidative stress, and the inflammatory response in subjects with hypertriglyceridemia and the metabolic syndrome

Robert S. Rosenson*, David A. Wolff, Anna L. Huskin, Irene B. Helenowski, Alfred W. Rademaker

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

89 Scopus citations

Abstract

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 in-flammatory responses, and these antiatherosclerotic effects were most highly correlated with reductions in large VLDL particles.

Original languageEnglish (US)
Pages (from-to)1945-1951
Number of pages7
JournalDiabetes care
Volume30
Issue number8
DOIs
StatePublished - Aug 2007

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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