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PPARα Activation with Fenofibrate Attenuates Diabetic Nephropathy in Zucker Diabetic Fatty Rats
Author(s) -
Li Lingyun,
Zhao Xueying
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.944.8
Subject(s) - fenofibrate , medicine , endocrinology , diabetic nephropathy , glomerulosclerosis , nephropathy , kidney , diabetes mellitus , proteinuria
Peroxisome proliferator–activated receptors (PPARs) are nuclear transcription factors and play an important role in lipid metabolism, glucose homeostasis and inflammation. PPARα is expressed in the kidney, and its agonists exhibit protective effects in type 2 diabetes. In the present study, we investigated the effect of the PPARα agonist fenofibrate on diabetic nephropathy in Zucker diabetic fatty (ZDF) rats. 12‐week‐old male Zucker lean and Zucker diabetic fatty rats were orally administered with fenofibrate (150mg/kg/day) or vehicle for 10 weeks. Treatment with fenofibrate had little effect on body weight gain and blood glucose in Zucker rats. Histological analysis revealed increased glomerular size and collagen deposition in the kidney of ZDF rats. Fenofibrate markedly reduced diabetic glomerular hypertrophy by 17.1%, attenuated collagen expansion by 48.2%, and improved glomerulosclerosis by 69.1%. Gelatin zymography showed MMP‐9 activity was increased in the plasma of ZDF rats, which was further induced by fenofibrate treatment. Furthermore, immunostaining indicated that the over‐expression of α‐smooth muscle actin in diabetic glomeruli and interstitials was significantly decreased by fenofibrate. In conclusion, activation of PPARα with fenofibrate may protect against diabetic nephropathy by attenuating glomerular hypertrophy, renal fibrosis and glomerulosclerosis in ZDF rats.