Faculty Collaboration Database

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 Oct 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 (requires institutional sign-in at Scopus site)   16 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 (SS^LepRmutant strain). At 6 wk of age, body weight was 35% higher in the SS^LepRmutant strain compared with SS_WT rats and remained elevated throughout the entire study. The SS^LepRmutant strain exhibited impaired glucose tolerance and increased plasma insulin levels at 6 wk of age, suggesting insulin resistance while SS_WT 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 SS^LepRmutant strain compared with SS_WT rats (201 ± 10 vs. 155 ± 3 mmHg, respectively). Interestingly, proteinuria was substantially higher at 6 wk of age in the SS^LepRmutant strain vs. SS_WT rats (241 ± 27 vs. 24 ± 2 mg/day, respectively) and remained elevated until the end of the study. The kidneys from the SS^LepRmutant strain displayed significant glomerular injury, including podocyte foot process effacement and lipid droplets compared with SS_WT rats as early as 6 wk of age. By 18 wk of age, plasma creatinine levels were twofold higher in the SS^LepRmutant strain vs. SS_WT rats, suggesting the presence of chronic kidney disease (CKD). Overall, these results indicate that the SS^LepRmutant 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 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