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Abstract: SA-PO439

Phenotypic Features of Advanced Nephropathy in a Murine Model of Metabolic Syndrome: Focus on Sex Differences

Session Information

Category: Diabetic Kidney Disease

  • 701 Diabetic Kidney Disease: Basic

Author

  • Prabhakar, Sharma S., Texas Tech University Health Sciences Center, Lubbock, Texas, United States
Background

Diabetes nephropathy (DN) which is often an integral part of obesity and metabolic syndrome (MS), is the most cmmon cause of ESRD in most countries..We had originally characterized nephropathy in ZSF rats, a rat model of DN and MS (Prabhakar S, JASN 2007). While male ZSF rats developed advanced features of DN and MS, the phenotypic features of female ZSF rats which have the same genetic background have not been well described.The goals of this study are to examine and compare the expression of MS in male and female ZSF rats at an advanced age.

Methods

Obese ZSF (ZDFxSHHF-fa/facp) model was developed by crossing lean female Zucker Diabetic Fatty (ZDF ./fa) and lean male Spontaneously Hypertensive Heart Failure (SHHF/Mcc-facp, ./fa) rats. Male and female CD rats were used as controls. Rats were monitored from 8th week of life and were fed normal rat chow (CD rats) or high calorie, high fat diet (Purina 5008) in the case of ZSF rats. The present report pertains to data obtained at 46 weeks of age. Blood pressure (BP) was measured by tail cuff plethysmography (Non-Invasive BP measurements using the Kent CODA system). Blood and urine were examined for glucose (Ascensia Contour glucometer) and protein levels. Body weights were measured weekly.

Results

The data here represent the results at 46th week in ZSF and CD rats, Obesity was first evident in ZSF rats at 20 wks but progressed steadily. Male ZSF rats were heavier than female ZSF rats ( 736±31 vs. 508±44gm p<0.0001) CD male rats were also heavier than female (802±111 vs. 306±31, p<0.0001) Male ZSF and CD rats did not differ significantly in their weights. Male ZSF rats developed significant hypertension compared to female rats (169/126 vs 139/89 p<0.05) CD males and female rats has similar BP (139±102 vs.136±90 mm/Hg p=NS). Proteinuria was was significantly high in male ZSF rats compared to female rats (>2 gm vs.1 gm) while CD rats had trace or no proteinuria. Male ZSF rats developed overt diabetes compared to mild diabetes in female ZSF rats.

Conclusion

These findings indicate that despite having similar genetic make-up, obese ZSF rats displayed major differenes in male and female sexes. In general male rats displayed more florrid features of metabolic syndrome. These observations warrant more intense investigations to explore the etiologic basis and factors to account for such differences between sexes.

Funding

  • Private Foundation Support