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


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Department of Cardiology, The Second Xiangya Hospital of Central South University, middle Ren-Min road No. 86, Changsha, Hunan 410011, PR China.
Shui-Ping
SP
Zhao
Jie
J
Wu
D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D002478:Cells, Cultured; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D011345:Fenofibrate / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008297:Male; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D000960:Hypolipidemic Agents; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D011345:Fenofibrate