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Effects of Gemfibrozil on the Progression of Proteinuria in Obese Dahl Salt‐Sensitive Rats
Author(s) -
Shields Corbin Anthony,
Poudel Bibek,
Browning Evan,
Williams Jan Michael
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.573.6
Subject(s) - gemfibrozil , endocrinology , medicine , dyslipidemia , fibrate , proteinuria , leptin , leptin receptor , triglyceride , kidney disease , obesity , mutant , kidney , chemistry , cholesterol , biochemistry , gene
The prevalence of obesity has increased dramatically within the last decade and is now considered an independent risk factor for chronic kidney disease (CKD). Recently, we reported that obese Dahl salt‐sensitive leptin receptor mutant (SS LepR mutant) rats exhibit dyslipidemia and renal injury independent of hyperglycemia that progresses to CKD. Interestingly, the kidneys from the SS LepR mutant strain displayed increased renal triglycerides and significant glomerular injury including podocyte foot process effacement and lipid droplets. Lipid‐lowering drugs such as fibrates have proven to be renoprotective in various models of kidney disease. Therefore, in the current study, we tested the effects of gemfibrozil, a fibrate, on the progression of renal injury in SS LepR mutant rats. Twelve‐week‐old SS WT and SS LepR mutant rats were separated into four groups (n=4 in each group): (1) SS WT and (2) SS LepR mutant rats treated with vehicle and (3) SS WT and (4) SS LepR mutant rats treated with gemfibrozil (200 mg/kg/day, orally, powdered food) for 4 weeks. Treatment with gemfibrozil had no effect on body weight or blood glucose levels in SS WT and SS LepR mutant rats. We observed greater than a 10‐fold increase in plasma triglyceride levels in the SS LepR mutant strain versus the values measured in SS WT rats (1265±380 and 117±19 mg/day, respectively). Gemfibrozil treatment significantly reduced plasma triglycerides by 64% in SS WT rats (41±20 mg/dL) and 57% in the SS LepR mutant strain (549±108 mg/dL). During the course of the study, proteinuria rose from 89±26 and 416±11 mg/day to 181±46 and 675±47 mg/day in SS and SS LepR mutant rats, respectively. Chronic treatment with gemfibrozil markedly decreased the progression of proteinuria by 52% in SS WT rats (87±17 mg/day) and 43% in the SS LepR mutant strain (385±75 mg/day). The kidneys from vehicle‐treated SS LepR mutant rats displayed significant glomerular injury with mesangial expansion and increased interstitial fibrosis and tubular protein casts compared to SS WT rats. Gemfibrozil treatment markedly decreased these renal abnormalities in both strains. These data indicate that reducing plasma lipid levels with gemfibrozil prevents the progression of proteinuria in both lean SS WT and obese SS LepR mutant rats. Support or Funding Information This study was supported by GM104357 and DK109133. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .