Fenofibrate reduces fasting and postprandial inflammatory responses among hypertriglyceridemia patients with the metabolic syndrome

Objective: To examine the effects of fenofibrate ( 160 mg/d) therapy on fasting and postprandial cytokine production in subjects with metabolic syndrome and hypertriglyceridemia. Research design and methods: Randomized, double-blind, controlled trial that compared the effects of 3-month therapy with placebo and fenolibrate on fasting and postprandial cytokine production in 55 subjects with metabolic syndrome and elevated fasting triglycerides (>= 1.7 and <6.78 mmol/L). Results: Fenofibrate treatment reduced concentrations of monohydroxy fatty acids (OH-FA) by 15.5% (p = 0.001), lipopolysaccharide activated monocyte chemotactic protein-1 (MCP-1/CCL2) production in fasting blood samples by 3.4% (p=0.01 vs. placebo), macrophage inflammatory protein-1 alpha (MIP-1 alpha/CCU) by 3.5% (p=0.01), and interleukin-1 beta (IL-1 beta) by 2.5% (p=0.04). After a standardized fat load (50kg/m(2)), OH-FA were reduced by 31.0% (p <0.0001), MCP-1/CCL2 was reduced by 5.2% (p=0.002), MIP-1 alpha/CCL3 by 3.9% (p=0.007), and IL-I beta by 3.4% (p=0.02). Reductions in MCP-1/CCL2, MIP-1 alpha/CCL3, and IL-1 beta production correlated with changes in fasting and postprandial large very low-density lipoprotein (VLDL) (all p < 0.005) and small low-density lipoprotein (LDL) particles (all p < 0.05). In stepwise regression models that included age, gender, weight change, and drug assignment, large VLDL particles were associated with reductions in postprandial MCP-1/CCL2 (p = 0.042), MIP-1 alpha/CCL3 (p = 0.003), and IL-1 beta (p = 0.02). Conclusions: This study reports that fenofibrate reduces whole blood production of inflammatory cytokines and hepatic-synthesized inflammatory proteins, and the anti-inflammatory effects of fenofibrate therapy involve VLDL- and LDL-mediated pathways. (C) 2008 Elsevier Ireland Ltd. All rights reserved.