Fenofibrate, a PPARα agonist, has renoprotective effects in mice by enhancing renal lipolysis

Kidney Int. 2011 Apr;79(8):871-82. doi: 10.1038/ki.2010.530. Epub 2011 Jan 26.


As renal lipotoxicity can lead to chronic kidney disease (CKD), we examined the role of peroxisome proliferator-activated receptor (PPAR)-α, a positive regulator of renal lipolysis. Feeding mice a high-fat diet induced glomerular injury, and treating them with fenofibrate, a PPARα agonist, increased the expression of lipolytic enzymes and reduced lipid accumulation and oxidative stress in glomeruli, while inhibiting the development of albuminuria and glomerular fibrosis. In mice given an overload of free fatty acid-bound albumin to induce tubulointerstitial injury, fenofibrate attenuated the development of oxidative stress, macrophage infiltration, and fibrosis, and enhanced lipolysis in the renal interstitium. Fenofibrate inhibited palmitate-induced expression of profibrotic plasminogen activator inhibitor-1 (PAI-1) in cultured mesangial cells, and the expression of both monocyte chemoattractant protein-1 and PAI-1 in proximal tubular cells along with the overexpression of lipolytic enzymes. Thus, fenofibrate can attenuate lipotoxicity-induced glomerular and tubulointerstitial injuries, with enhancement of renal lipolysis. Whether amelioration of renal lipotoxicity by PPARα agonists will turn out to be a useful strategy against CKD will require direct testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Base Sequence
  • Cells, Cultured
  • Chemokine CCL2 / metabolism
  • DNA Primers / genetics
  • Dietary Fats / administration & dosage
  • Disease Models, Animal
  • Fenofibrate / pharmacology*
  • Kidney / drug effects*
  • Kidney / metabolism*
  • Lipolysis / drug effects*
  • Lipolysis / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • PPAR alpha / agonists*
  • PPAR alpha / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Renal Insufficiency, Chronic / drug therapy
  • Renal Insufficiency, Chronic / etiology
  • Renal Insufficiency, Chronic / metabolism
  • Serpin E2 / genetics
  • Serpin E2 / metabolism
  • Serum Albumin, Bovine / administration & dosage


  • Anti-Inflammatory Agents
  • Ccl2 protein, mouse
  • Chemokine CCL2
  • DNA Primers
  • Dietary Fats
  • PPAR alpha
  • RNA, Messenger
  • Serpin E2
  • Serpine2 protein, mouse
  • Serum Albumin, Bovine
  • Fenofibrate