Effect of fenofibrate on adiponectin and inflammatory biomarkers in metabolic syndrome patients.
Adiponectin is an adipose-secreted hormone with anti-inflammatory properties mediated by inhibition of nuclear factor-kappaB (NF-kappaB) signaling. This study investigates whether fenofibrate alters adiponectin levels in patients with hypertriglyceridemia and the metabolic syndrome, and examines the association of adiponectin with circulating inflammatory markers and whole blood cytokine production. The effects of fenofibrate (160 mg/day) on adiponectin and other inflammatory markers were investigated in a 12-week randomized, placebo-controlled trial in 55 patients with hypertriglyceridemia (plasma triglycerides > or =1.7 mmol/l and <6.8 mmol/l), central obesity and other characteristics of the metabolic syndrome who were not receiving lipid-altering therapies. In the fenofibrate group, adiponectin levels increased from 4.10 to 4.50 microg/ml (+7.7%); in the placebo group, adiponectin levels increased by 1.8%; (P = 0.0005). In multivariate models including age, gender, and waist circumference, there were inverse correlations between changes in adiponectin and vascular cell adhesion molecule-1 (VCAM-1) (r = -0.54, P < 0.0001) and intercellular adhesion molecule-1 (ICAM-1) (r = -0.57, P < 0.0001), and C-reactive protein (CRP) (r = -0.40, P = 0.0041); lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-alpha (TNF-alpha) (r = -0.30, P = 0.035), interleukin (IL)-1beta (r = -0.44, P = 0.0016), monocyte chemotactic protein-1 (MCP-1) (r = -0.46, P = 0.001), and macrophage inflammatory protein-1alpha (MIP-1alpha) (r = -0.45, P = 0.0012). Fenofibrate (160 mg/day) raised adiponectin levels in patients with hypertriglyceridemia and the metabolic syndrome. Changes in adiponectin were significantly and inversely associated with changes in multiple inflammatory markers. These data suggest that adiponectin may contribute to the anti-inflammatory effects of fenofibrate.
Rosenson
Robert S
RS
Department of Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan, USA. rrosenso@umich.edu
D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood*; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
D052242:Adiponectin; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D000960:Hypolipidemic Agents; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D005340:Fibrinogen; D002097:C-Reactive Protein; D011345:Fenofibrate