PPARα agonist fenofibrate improves diabetic nephropathy in db/db mic

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

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

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
Volume69
Issue number9
DOIs
Publication statusPublished - 2006 May 1
Externally publishedYes

Fingerprint

Fenofibrate
Peroxisome Proliferator-Activated Receptors
Diabetic Nephropathies
Mesangial Cells
Type 2 Diabetes Mellitus
Hypertrophy
Insulin Resistance
Insulin
Diet
Kidney
Albuminuria
Cytoplasmic and Nuclear Receptors
Collagen Type I
Islets of Langerhans
Lipid Metabolism
Hyperglycemia
Blood Glucose
Albumins
Cultured Cells
Fasting

Keywords

  • Diabetic nephropathy
  • Fenofibrate
  • PPARα
  • Type II diabetes

ASJC Scopus subject areas

  • Nephrology

Cite this

Park, C. W., Zhang, Y., Zhang, X., Wu, J., Chen, L., Cha, D-R., ... Guan, Y. (2006). PPARα agonist fenofibrate improves diabetic nephropathy in db/db mic. Kidney International, 69(9), 1511-1517. https://doi.org/10.1038/sj.ki.5000209

PPARα agonist fenofibrate improves diabetic nephropathy in db/db mic. / Park, C. W.; Zhang, Y.; Zhang, X.; Wu, J.; Chen, L.; Cha, Dae-Ryong; Su, D.; Hwang, M. T.; Fan, X.; Davis, L.; Striker, G.; Zheng, F.; Breyer, M.; Guan, Y.

In: Kidney International, Vol. 69, No. 9, 01.05.2006, p. 1511-1517.

Research output: Contribution to journalArticle

Park, CW, Zhang, Y, Zhang, X, Wu, J, Chen, L, Cha, D-R, Su, D, Hwang, MT, Fan, X, Davis, L, Striker, G, Zheng, F, Breyer, M & Guan, Y 2006, 'PPARα agonist fenofibrate improves diabetic nephropathy in db/db mic', Kidney International, vol. 69, no. 9, pp. 1511-1517. https://doi.org/10.1038/sj.ki.5000209
Park, C. W. ; Zhang, Y. ; Zhang, X. ; Wu, J. ; Chen, L. ; Cha, Dae-Ryong ; Su, D. ; Hwang, M. T. ; Fan, X. ; Davis, L. ; Striker, G. ; Zheng, F. ; Breyer, M. ; Guan, Y. / PPARα agonist fenofibrate improves diabetic nephropathy in db/db mic. In: Kidney International. 2006 ; Vol. 69, No. 9. pp. 1511-1517.
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