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

26 Citations (Scopus)

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

Fingerprint

Zucker Rats
Estrogens
Wounds and Injuries
Ovariectomy
Albuminuria
Desmin
Collagen Type IV
Hyperinsulinism
Apolipoproteins B
Hyperlipidemias
Fibronectins
Lipoproteins
Renal Insufficiency
Albumins
Triglycerides
Obesity
Macrophages
Cholesterol
Kidney

Keywords

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

ASJC Scopus subject areas

  • Nephrology

Cite this

Estrogen worsens incipient hypertriglyceridemic glomerular injury in the obese Zucker rat. / Stevenson, Frazier T.; Wheeldon, Carrie M.; Gades, Matthew D.; Kaysen, George; Stern, Judith S.; Van Goor, Harry.

In: Kidney International, Vol. 57, No. 5, 2000, p. 1927-1935.

Research output: Contribution to journalArticle

Stevenson, Frazier T. ; Wheeldon, Carrie M. ; Gades, Matthew D. ; Kaysen, George ; Stern, Judith S. ; Van Goor, Harry. / Estrogen worsens incipient hypertriglyceridemic glomerular injury in the obese Zucker rat. In: Kidney International. 2000 ; Vol. 57, No. 5. pp. 1927-1935.
@article{d420b8daed3b44c8a8c8639ff04748bf,
title = "Estrogen worsens incipient hypertriglyceridemic glomerular injury in the obese Zucker rat",
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.",
keywords = "Estrogen replacement therapy, Glomerulosclerosis, Hypertriglyceridemia, Progressive renal disease",
author = "Stevenson, {Frazier T.} and Wheeldon, {Carrie M.} and Gades, {Matthew D.} and George Kaysen and Stern, {Judith S.} and {Van Goor}, Harry",
year = "2000",
doi = "10.1046/j.1523-1755.2000.00042.x",
language = "English (US)",
volume = "57",
pages = "1927--1935",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Estrogen worsens incipient hypertriglyceridemic glomerular injury in the obese Zucker rat

AU - Stevenson, Frazier T.

AU - Wheeldon, Carrie M.

AU - Gades, Matthew D.

AU - Kaysen, George

AU - Stern, Judith S.

AU - Van Goor, Harry

PY - 2000

Y1 - 2000

N2 - 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.

AB - 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.

KW - Estrogen replacement therapy

KW - Glomerulosclerosis

KW - Hypertriglyceridemia

KW - Progressive renal disease

UR - http://www.scopus.com/inward/record.url?scp=0034022991&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034022991&partnerID=8YFLogxK

U2 - 10.1046/j.1523-1755.2000.00042.x

DO - 10.1046/j.1523-1755.2000.00042.x

M3 - Article

C2 - 10792611

AN - SCOPUS:0034022991

VL - 57

SP - 1927

EP - 1935

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 5

ER -