title: Effect of clofibrate on fatty acid metabolism in the kidney of puromycin-induced nephrotic rats.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of General Medicine and Rehabilitation, Tohoku Medical and Pharmaceutical University School of Medicine, 1-12-1 Fukumuro, Miyagino-ku, Sendai, 983-8512, Japan. ymuroya@hosp.tohoku-mpu.ac.jp.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Muroya
authors.affiliation: Department of Internal Medicine and Rehabilitation Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Ito
mesh_terms: D000818:Animals; D002994:Clofibrate / Q000494:pharmacology*; D005227:Fatty Acids / Q000378:metabolism*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000473:pathology; D008297:Male; D009404:Nephrotic Syndrome / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D047493:PPAR alpha / Q000819:agonists; D011691:Puromycin / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000032:analysis; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D002994:Clofibrate; D005227:Fatty Acids; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D011691:Puromycin; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor
keywords: Clofibrate; Fatty acid metabolism; Lipotoxicity; Proteinuria