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Clinical and Experimental Nephrology

, Volume 20, Issue 6, pp 862–870 | Cite as

Effect of clofibrate on fatty acid metabolism in the kidney of puromycin-induced nephrotic rats

  • Yoshikazu MuroyaEmail author
  • Osamu Ito
Original Article

Abstract

Background

Proteinuria plays an essential role in the progression of tubulointerstitial damage, which causes end-stage renal disease. An increased load of fatty acids bound to albumin reabsorbed into proximal tubular epithelial cells (PTECs) contributes to tubulointerstitial damage. Fibrates, agonists of peroxisome proliferator-activated receptor α (PPARα), have renoprotective effects against proteinuria whereas the effects of these compounds on fatty acid metabolism in the kidney are still unknown. Therefore, the present study examined whether the renoprotective effects of clofibrate were associated with improvement of fatty acid metabolism in puromycin aminonucleoside (PAN)-induced nephrotic rats.

Methods

Rats were allocated to the control, PAN or clofibrate-treated PAN group. Biochemical parameters, renal injury and changes in fatty acid metabolism were studied on day14.

Results

PAN increased proteinuria, lipid accumulation in PTECs, excretions of N-acetyl-β-d-glucosaminidase (NAG) and 8-hydroxydeoxyguanosine (8OHdG) and the area of caspase 3-positive tubular cells. It decreased renal expressions of medium-chain acyl-CoA dehydrogenase (MCAD), cytochrome P450 (CYP)4A, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) and estrogen-related receptor α (ERRα) without change of the expression of PPARα. Clofibrate reduced proteinuria, lipid accumulation, NAG excretion and the area of caspase 3-positive tubular cells. However, albumin excretion was not reduced and 8OHdG excretion was increased. Clofibrate minimized changes in MCAD, CYP4A, PGC-1α and ERRα expressions with increased PPARα, very long-chain acyl-CoA dehydrogenase (VLCAD) and long-chain acyl-CoA dehydrogenase (LCAD) expressions.

Conclusion

Clofibrate is protective against renal lipotoxicity in PAN nephrosis. This study indicates that clofibrate has renoprotective effects through maintaining fatty acid metabolism in the kidney of PAN-induced nephrotic rats.

Keywords

Proteinuria Lipotoxicity Clofibrate Fatty acid metabolism 

Notes

Acknowledgments

This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology (Nos. 20590694 and 20300184). We thank Dr. Stanley V. Smith and Dr. Richard J. Roman (University of Mississippi Medical Center) for helping to edit this manuscript.

Compliance with ethical standards

Significant financial interests

None.

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Copyright information

© Japanese Society of Nephrology 2016

Authors and Affiliations

  1. 1.Department of General Medicine and RehabilitationTohoku Medical and Pharmaceutical University School of MedicineSendaiJapan
  2. 2.Department of Internal Medicine and Rehabilitation ScienceTohoku University Graduate School of MedicineSendaiJapan

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