Estrogen worsens incipient hypertriglyceridemic glomerular injury in the obese Zucker rat

Frazier T. Stevenson, Carrie M. Wheeldon, Matthew D. Gades, George Kaysen, Judith S. Stern, Harry Van Goor

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Background. The obese Zucker rat (OZR) is a model of glomerulosclerosis and renal failure in the setting of hyperlipidemia, hyperinsulinemia, and obesity. Our prior work in OZRs has shown that ovariectomy attenuates glomerulosclerosis, while added estrogen worsens it. To investigate the mechanism of estrogen's effects on glomerular disease in this model, we evaluated the effects of ovariectomy and estrogen supplementation on seven- week peripubertal OZRs. At this time point, rats exhibit no overt histologic glomerular disease, but are just beginning to show elevated urinary albumin excretion. Methods. Female OZRs fed ad libitum were ovariectomized at four weeks, with or without estrogen supplementation to raise estrogen levels to just below those of preoestral adults (mean 16.5 pg/mL). Sham-operated controls were included. Results. Ovariectomy normalized albuminuria, lowered total and very low-density lipoprotein triglycerides, and reduced glomerular fibronectin expression. Estrogen supplementation worsened albuminuria and raised total/very low-density lipoprotein triglycerides and total cholesterol. Estrogen-supplemented rats exhibited enhanced glomerular deposition of apo A-IV and apo B, increased glomerular expression of desmin and type IV collagen, and increased interstitial macrophage deposition. Conclusion. Estrogen may be permissive for the early development of renal disease in OZRs and may act by increasing triglyceride-rich lipoproteins, which then bind to glomerular cells and initiate or accelerate glomerulosclerosis.

Original languageEnglish (US)
Pages (from-to)1927-1935
Number of pages9
JournalKidney International
Volume57
Issue number5
DOIs
StatePublished - 2000

Keywords

  • Estrogen replacement therapy
  • Glomerulosclerosis
  • Hypertriglyceridemia
  • Progressive renal disease

ASJC Scopus subject areas

  • Nephrology

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