Gender differences in phenotypic expressions of metabolic syndrome in ZSF rats

Abstract

Aims: The focus of our laboratory has been to examine the mechanisms of insulin resistance and renal injury in metabolic syndrome. ZSF rats represent a transgenic murine model of human metabolic syndrome and spontaneously develop obesity, hyperglycemia, hypertension, progressive proteinuria, azotemia and severe hyperlipidemia. The renal and metabolic abnormalities in ZSF rats were first characterized and published from our laboratory (J Am Soc Neph 2007). However only male rats were examined in that study. Despite a totally similar genetic background, there could be significant gender differences in the expression of phenotypic characteristics of disease states. We examined the differences in the general and metabolic features of male and female rat models of metabolic syndrome. Methods: We studied male and female ZSF rats, an established model of metabolic syndrome. 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 the 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 between 15-20 weeks of age. Blood pressure was measured by tail cuff plethysmography (Non-Invasive Blood Pressure measurements using the Kent CODA system). Blood and urine were examined for glucose (Ascensia Contour glucometer) and protein levels. Body weights were measured every week. Results: Our results show that at 20 weeks, males were heavier than the females in both ZSF (545±26g vs. 401±42g p<0.05) and CD (608±73g vs. 301±22g p<0.05) strains of rats. ZSF female rats were heavier than CD female rats. Male ZSF rats were fatter than male CD rats although the latter appear larger (no statistical difference in weights). There were no statistically significant differences in the BP amongst the four groups, which were all in the normal range. Blood glucose level were elevated in ZSF compared to CD rats. Male ZSF rats had higher glucose levels (342±36 mg/dl) compared to female ZSF rats (95±16mg/dl, p<0.05). Urine glucose levels were higher in male ZSF rats while urine protein levels were higher in female ZSF rats compared to the other three groups. Conclusions: Although the male and female ZSF rats shared the same general genetic material, at 20 weeks of age they exhibited significant differences in various manifestations of metabolic syndrome with male ZSF rats exhibiting more advanced featues. These observations underscore the impact of gender and implied physiological factors in influencing the physical manifestations of a disease state. Private Research Endowment This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.