Abstract P020: Decreased Survival Rate in Female Obese Leptin Receptor Mutant Dahl Salt-Sensitive Rats that Develop Chronic Kidney Disease
Obesity contributes to sex differences in the risk for chronic kidney disease (CKD) in which males tend to develop CKD earlier in life than females. Therefore, in the current study, we examined whether there were sex differences in the development of CKD in the obese leptin receptor mutant Dahl salt-sensitive (SSLepRmutant) strain which was derived from Zinc-finger nucleases. We observed an increase in body weight in both female and male SSLepRmutant rats when compared to SS rats throughout the study. Glucose tolerance was impaired significantly in female and male SSLepRmutant rats versus SSrats by 18 weeks of age. The SSLepRmutant strain also developed hyperinsulinemia in comparison to their lean SS counterparts (6.86±0.83 vs 0.72±0.04 ng/mL, respectively, n=6). However, blood glucose in the SSLepRmutant strain remained within normal range throughout the course of the study regardless of sex. Female and male SSLepRmutant rats developed severe systolic hypertension (via tail-cuff) by 18 weeks of age when compared to the values measured in SS rats (199±7 and 201±10 vs. 159±5 and 155±4 mmHg, respectively, n=6). Yet, the rise in arterial pressure occurred earlier in female SSLepRmutant rats than males. Protein excretion was significantly higher in the SSLepRmutant strain as opposed to the values observed in SS rats at 18 weeks of age regardless of sex (488±61 and 631±86 vs. 50±17 and 149±23 mg/day, respectively, n=6). At the end of study, kidneys from the SSLepRmutant strain displayed increased glomerulosclerosis and interstitial fibrosis than SS rats. Female and male SSLepRmutant rats had a significant increase in plasma creatinine levels and averaged 2.1±0.4 mg/dL (n=6) compared to the normal value of 0.5±0.1 mg/dL (n=6) observed in the SS strain suggesting the presence of severe CKD. While both, female and male, SS rats survived the length of study, the survival rate of female SSLepRmutant rats was markedly reduced compared to their male counterparts (62%, 21 of 34 vs. 25%, 6 of 24, respectively). Overall, these data indicate that the SSLepRmutant strain may be a useful model to study sex differences during the development of CKD associated with obesity.
Author Disclosures: K. McPherson: None. D. Guillory: None. L. Taylor: None. D. Spires: None. A.C. Johnson: None. M.R. Garrett: None. J.M. Williams: B. Research Grant (includes principal investigator, collaborator, or consultant and pending grants as well as grants already received); Significant; AHA 12SDG9440034, NIGMS NIH P20GM104357.
This research has received full or partial funding support from the American Heart Association, Greater Southeast Affiliate (Alabama, Florida, Georgia, Louisiana, Mississippi, Puerto Rico & Tennessee).
- © 2015 by American Heart Association, Inc.