Fenofibrate reduces tumor necrosis factor-alpha serum concentration and adipocyte secretion of hypercholesterolemic...

Tumor necrosis factor-alpha (TNF-alpha) 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-alpha concentration and TNF-alpha 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-alpha 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-alpha concentration by 44.7% in fenofibrate treated group compared with high cholesterol group (P<0.05). The decreased levels of TNF-alpha correlated with the weight loss (r=0.35, P<0.05). Fenofibrate (10 to 100 micromol/l) significantly reduced release of TNF-alpha in adipocytes (P<0.05). Meanwhile serum TNF-alpha concentration were significantly correlated with TNF-alpha secretion in adipocytes (r=0.51, P<0.05).

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