title: Ezetimibe ameliorates early diabetic nephropathy in db/db mice.
abstract: OBJECTIVE
  Lipid-lowering medications have been suggested to have a potential benefit in the treatment of chronic kidney disease (CKD) such as diabetic nephropathy. Although ezetimibe has been widely used to lower serum cholesterol levels, the effect of this drug on diabetic nephropathy remains unclear. In the present study, therefore, we examined the protective effect of ezetimibe on diabetic nephropathy in db/db mice.
  
  
  METHODS
  Db/db mice were fed a standard diet with 0.01% (w/w) of ezetimibe for 8 weeks from 8 weeks of age.
  
  
  RESULTS
  Treatment with ezetimibe did not affect food intake, body weight gain, adiposity, or blood pressure in db/db mice. Ezetimibe also had no effect on glucose metabolism such as fasting plasma glucose and insulin; however, it markedly reduced plasma lipid levels and hepatic lipid contents and reduced the urinary excretion of albumin by 50% in db/db mice, suggesting the effect of ezetimibe on diabetic nephropathy. Furthermore, ezetimibe improved glomerular hypertrophy. Although ezetimibe had no effect on oxidative stress measured by urinary 8-OHdG in db/db mice, the plasma adiponectin level was normalized, and the expression of adiponectin receptor 1 in the kidney was increased by ezetimibe treatment.
  
  
  CONCLUSIONS
  Our data suggest that ezetimibe can improve early diabetic nephropathy through its hypolipidemic effect, and the amelioration of adiponectin resistance may also be responsible for the renoprotective effect of ezetimibe as its underlying mechanism.
authors.affiliation: Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tamura
authors.forename: Toshinori
authors.initials: T
authors.lastname: Murayama
authors.forename: Manabu
authors.initials: M
authors.lastname: Minami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsubara
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yokode
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
mesh_terms: D052242:Adiponectin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000517:prevention & control*; D000069438:Ezetimibe; D005919:Glomerular Filtration Rate; D007249:Inflammation / Q000188:drug therapy*; D007677:Kidney Function Tests; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008661:Metabolism, Inborn Errors / Q000188:drug therapy*; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000503:physiopathology*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C475418:ADIPOR1 protein, human; D052242:Adiponectin; D000924:Anticholesteremic Agents; D001384:Azetidines; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D003404:Creatinine; D000069438:Ezetimibe