Estrogen accelerates the development of renal disease in female obese Zucker rats

Renal failure is the primary cause of death in obese Zucker rats (OZR). We previously found that renal injury occurred earlier and with greater severity in female OZR; also, prevention of hyperphagia decreased renal damage in females more than males. To examine the relationship between estrogen (E), hyperphagia, hyperlipidemia, and renal injury in female OZR, we studied four groups from 5 to 10 or 21 weeks of age: Sham-operated (Sham), ovariectomized (Ovx), Ovx with estrogen treatment (Ovx+E), and, since Ovx increases food intake, Ovx pair-fed to sham (Ovx-PF). By only six weeks of age, albumin excretion (UAE) increased significantly in Ovx+E (9.9 +/- 4.1 mg/day). Ovx+E also ate least and gained the least weight, bur had the highest plasma lipid levels. In contrast, UAE in Ovx did not increase by 10 weeks of age, despite a significantly greater food consumption. The hyperlipidemia of Ovx+E was due primarily to triglycerides. Both plasma triglycerides and renal injury, judged from either histology or UAE, were greatest in the Ovx+E group. Fasting plasma glucose was lower and insulin was higher in Ovx+E compared to Ovx rats at 15 weeks of age. Estrogen may promote renal injury in female OZR by increasing the plasma concentration of triglyceride-rich lipoproteins.