#3976 THE ROLE OF GENDER DIFFERENCES AND MENOPAUSE IN OBESITY-RELATED RENAL DISEASE, RENAL INFLAMMATION AND LIPOTOXICITY

Abstract

Abstract Background and Aims The pathogenesis of obesity related-renal disease is unknown. Gender differences may have a role in renal damage in obesity. In particular, menopause can promote renal disease in obese women. In a previous study we observed that obese male and female mice developed albuminuria, hyperfiltration and glomerulomegaly, and these changes were more severe in those obese ovariectomized females. In this study we evaluated renal inflammation and lipotoxicity in that model. Method Twenty-two males and 57 females C57BL6/J mice were randomized to standard diet (SD) or high fat diet (HFD) for six months. A group of female animals on SD o HFD was ovariectomized to induce menopause. In renal tissue we evaluated cytokines: NF-κβ, IL-1β, MCP-1, TNF-α and total lipid content, lipid classes, fatty acid profile and fatty acids in lipid classes. Part of the lipidomic analysis was performed in urine. Results Obese males and females showed higher NF-κβ, TNF-α and MCP-1 in renal tissue (Fig. 1). Obese females ovariectomized had higher IL-1β and TNF-α compared with obese female not-ovariectomized (Fig. 1B). Obese animals showed lower pro-inflammatory fatty acids (16:0, 16:1n-7 and 18:2n-6) and higher anti-inflammatory fatty acid (22:6 n-3) (Fig. 2A). This pattern was also observed in specific lipid classes and urine. Finally, obese females ovariectomized had a more exacerbated pattern, with high 18:0 in phosphatidylcholine, high 18:0 DMA phosphatidylethanolamine and low 16:0 in triglycerides (Fig. 2B-D). Conclusion In conclusion, obesity induces inflammation and an unbalanced (pro-inflammatory) lipidic profile in renal tissue. This pattern seems to be enhanced in obesity after menopause.