Fenofibrate reduces fasting and postprandial inflammatory responses among hypertriglyceridemia patients with the metabolic syndrome.
OBJECTIVE
To examine the effects of fenofibrate (160mg/d) therapy on fasting and postprandial cytokine production in subjects with metabolic syndrome and hypertriglyceridemia.


METHODS
Randomized, double-blind, controlled trial that compared the effects of 3-month therapy with placebo and fenofibrate on fasting and postprandial cytokine production in 55 subjects with metabolic syndrome and elevated fasting triglycerides (>or=1.7 and <6.78mmol/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-1alpha (MIP-1alpha/CCL3) by 3.5% (p=0.01), and interleukin-1beta (IL-1beta) 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-1alpha/CCL3 by 3.9% (p=0.007), and IL-1beta by 3.4% (p=0.02). Reductions in MCP-1/CCL2, MIP-1alpha/CCL3, and IL-1beta 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-1alpha/CCL3 (p=0.003), and IL-1beta (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.
Rosenson
Robert S
RS
Division of Cardiovascular Medicine, University of Michigan, Domino's Farms, 24 Frank Lloyd Wright Drive, Lobby A, Ann Arbor, MI 48106-0736, USA. rrosenso@umich.edu
Huskin
Anna L
AL
Wolff
David A
DA
Helenowski
Irene B
IB
Rademaker
Alfred W
AW
D000368:Aged; D016207:Cytokines / Q000097:blood*; D004311:Double-Blind Method; D005215:Fasting; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D019518:Postprandial Period; D016896:Treatment Outcome
D016207:Cytokines; D000960:Hypolipidemic Agents; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011345:Fenofibrate