PPARα agonist fenofibrate improves diabetic nephropathy in db/db mic

C. W. Park, Y. Zhang, X. Zhang, J. Wu, L. Chen, D. R. Cha, D. Su, M. T. Hwang, X. Fan, L. Davis, G. Striker, F. Zheng, M. Breyer, Y. Guan

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171 Citations (Scopus)


Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily, and plays an important role in lipid metabolism and glucose homeostasis. The purpose of this study is to determine whether the activation of PPARα by fenofbrate would improve diabetes and its renal complications in type II diabetes mellitus. Male C57 BLKS db/db mice and db/m controls at 8 weeks of age were divided to receive either a regular diet chow (db/db, n = 8; db/m, n = 6) or a diet containing fenofibrate (db/db, n = 8; db/m, n = 7). Mice were followed for 8 weeks. Fenofibrate treatment dramatically reduced fasting blood glucose (P < 0.001) and HbA1c levels (P < 0.001), and was associated with decreased food intake (P < 0.01) and slightly reduced body weight. Fenofibrate also ameliorated insulin resistance (P < 0.001) and reduced plasma insulin levels (P < 0.05) in db/db mice. Hypertrophy of pancreatic islets was decreased and insulin content markedly increased (P < 0.05) in fenofibrate-treated diabetic animals. In addition, fenofibrate treatment significantly reduced urinary albumin excretion (P < 0.001). This was accompanied by dramatically reduced glomerular hypertrophy and mesangial matrix expansion. Furthermore, the addition of fenofibrate to cultured mesangial cells, which possess functional active PPARα, decreased type I collagen production. Taken together, the PPARα agonist fenofibrate dramatically improves hyperglycemia, insulin resistance, albuminuria, and glomerular lesions in db/db mice. The activation of PPARα by fenofibrate in mesangial cells may partially contribute to its renal protection. Thus, fenofibrate may serve as a therapeutic agent for type II diabetes and diabetic nephropathy.

Original languageEnglish
Pages (from-to)1511-1517
Number of pages7
JournalKidney International
Issue number9
Publication statusPublished - 2006 May
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by NIH, Genzyme Renal Innovations Program and NNSF of China.

Funding Information:
We thank Drs Kumar Sharma and Steve Dunn and the AMDCC U01 for help in measuring serum creatinine. These studies were supported by the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) DK065074-02 (to YG), DK64118 (to FZ) and P01-DK 38226 (to MDB), and a funding from the Genzyme Renal Innovations Program and the NNSF of China (30271521 and 104001) (to YG).


  • Diabetic nephropathy
  • Fenofibrate
  • PPARα
  • Type II diabetes

ASJC Scopus subject areas

  • Nephrology


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