Tumor necrosis factor-α (TNF-α) is produced by cells of the macrophage–monocyte lineage and by adipocytes. It may provide the link between inflammation and atherosclerosis. The aim of this study was to evaluate the effect of fenofibrate on serum TNF-α concentration and TNF-α secretion by adipocytes from hypercholesterolemic rabbits.

Ten male New Zealand white rabbits were fed with high-cholesterol diet for 8 weeks, and were randomly divided into two groups: (1) high cholesterol group: maintained cholesterol diet for 4 weeks; and (2) fenofibrate treated group: the same cholesterol diet supplemented with fenofibrate (30 mg/kg/day) for 4 weeks. Control group was fed with normal diet for 12 weeks. Subcutaneous adipose was collected for adipocytes culture. TNF-α concentrations in serum and adipocytes culture supernatant were measured by ELISA.

Rabbits fed with high-cholesterol diet showed higher serum levels of total cholesterol, low density lipoprotein cholesterol than those fed with normal diet (P<0.001). Fenofibrate treatment did not change serum lipid levels during the feeding period, but decreased high cholesterol diet-induced increases in body weight by 19% and serum TNF-α concentration by 44.7% in fenofibrate treated group compared with high cholesterol group (P<0.05). The decreased levels of TNF-α correlated with the weight loss (r=0.35, P<0.05). Fenofibrate (10 to 100 μmol/l) significantly reduced release of TNF-α in adipocytes (P<0.05). Meanwhile serum TNF-α concentration were significantly correlated with TNF-α secretion in adipocytes (r=0.51, P<0.05).

Our study indicated that fenofibrate reduced tumor necrosis factor-α serum concentration and adipocyte secretion of hypercholesterolemic rabbits. This effect of fenofibrate might contribute to its benefits on the prevention and treatment of atherosclerosis.