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

Abstract

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, but 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.

Hyperphagia as a Mediator of Renal Disease Initiation in Obese Zucker Rats

“…However, we do consider them to be less likely than hypertriglyceridemia. Previous work has shown the direct effects of hormones, such as estrogen, insulin, and leptin, on renal injury to be unimportant or less important than triglycerides (4,6,9). Although renal hemodynamics are often critical in the rate of progression of renal disease, we consider this to be an unlikely explanation for the salutary effect of pair-feeding in OZRs.…”

“…Ovariectomy of the female rat markedly reduces renal disease (6,9). Estrogen acts independent of diet to increase serum triglycerides and VLDL, and UAE correlates better with serum triglycerides than with estrogen level, suggesting that the protective effect of ovariectomy also may be due to its lipid-lowering effects (6).…”

“…Water and moistened food were available. UAE was determined using electroimmunodiffusion using rabbit anti-rat albumin and purified rat albumin as previously described (9). UAE was performed weekly from 6 to 10 weeks of age.…”

Dyslipoproteinemia and Impairment of Renal Function in Diabetic Kidney Disease: An Analysis of Animal Studies, Observational Studies, and Clinical Trials

“…In humans, VLDL secreted by the liver contains ApoB-100 while, in rat, VLDL secreted by rat liver may also contain ApoB-48, which could be taken up by various tissues including mesangial cells [28]. There is also gender difference in the models [62].…”

Effects of Estrogen Replacement Therapy to the Renal Function in Postmenopausal Women

“…Kardiyovasküler mortalite ile iliflkisi ayn› zamanda diabetik olmayan hastalarda ve Tip II DM'lu hastalarda da rapor edilmifltir (18,26) . (6,23,24) .…”