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Early development of podocyte injury independently of hyperglycemia and elevations in arterial pressure in nondiabetic obese Dahl SS leptin receptor mutant rats. Am J Physiol Renal Physiol 2016 10 01;311(4):F793-F804

Date

07/29/2016

Pubmed ID

27465994

Pubmed Central ID

PMC5142236

DOI

10.1152/ajprenal.00590.2015

Scopus ID

2-s2.0-84989932218   2 Citations

Abstract

The current study examined the effect of obesity on the development of renal injury within the genetic background of the Dahl salt-sensitive rat with a dysfunctional leptin receptor derived from zinc-finger nucleases (SSLepRmutant strain). At 6 wk of age, body weight was 35% higher in the SSLepRmutant strain compared with SSWT rats and remained elevated throughout the entire study. The SSLepRmutant strain exhibited impaired glucose tolerance and increased plasma insulin levels at 6 wk of age, suggesting insulin resistance while SSWT rats did not. However, blood glucose levels were normal throughout the course of the study. Systolic arterial pressure (SAP) was similar between the two strains from 6 to 10 wk of age. However, by 18 wk of age, the development of hypertension was more severe in the SSLepRmutant strain compared with SSWT rats (201 ± 10 vs. 155 ± 3 mmHg, respectively). Interestingly, proteinuria was substantially higher at 6 wk of age in the SSLepRmutant strain vs. SSWT rats (241 ± 27 vs. 24 ± 2 mg/day, respectively) and remained elevated until the end of the study. The kidneys from the SSLepRmutant strain displayed significant glomerular injury, including podocyte foot process effacement and lipid droplets compared with SSWT rats as early as 6 wk of age. By 18 wk of age, plasma creatinine levels were twofold higher in the SSLepRmutant strain vs. SSWT rats, suggesting the presence of chronic kidney disease (CKD). Overall, these results indicate that the SSLepRmutant strain develops podocyte injury and proteinuria independently of hyperglycemia and elevated arterial pressure that later progresses to CKD.

Author List

McPherson KC, Taylor L, Johnson AC, Didion SP, Geurts AM, Garrett MR, Williams JM

Author

Aron Geurts PhD Associate Professor in the Physiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Arterial Pressure
Blood Glucose
Hyperglycemia
Kidney
Male
Obesity
Podocytes
Rats
Rats, Inbred Dahl
Rats, Transgenic
Receptors, Leptin
Renal Insufficiency, Chronic
jenkins-FCD Prod-468 69a93cef3257f26b866d455c1d2b2d0f28382f14