Gene expression profiling of orbital adipose tissue from patients with Graves' ophthalmopathy

A potential role for secreted frizzled-related protein-1 in orbital adipogenesis

Seema Kumar, Alexey Leontovich, Michael J. Coenen, Rebecca S. Bahn

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

Context: The signs and symptoms of Graves' ophthalmopathy (GO) result from inflammation and increased volume of the orbital adipose tissues and extraocular muscles. Objective: Our objective was to identify differentially regulated genes that may be involved in stimulating the orbital adipose tissue expansion seen in GO. Design: Gene expression profiling was used to compare genes expressed in orbital adipose tissues from GO patients and normal individuals. Setting: The study took place at a private practice tertiary referral center. Patients: Orbital adipose tissues were collected at transantral orbital decompression surgery from 20 euthyroid patients undergoing this procedure for severe GO and at early autopsy from eight normal individuals having no evidence of thyroid or ocular disease. Results: Of the 12,686 genes analyzed, 25 known genes were increased in expression (>4-fold) in GO orbital tissues, whereas 11 genes were decreased (>4-fold). Up-regulated genes, confirmed by quantitative RT-PCR, included secreted frizzled-related protein-1 (sFRP-1; 18.5-fold) and several adipocyte-related genes, including peroxisome proliferator activated receptor-γ(44.1-fold) and adiponectin (25-fold). Treatment in vitro of GO orbital preadipocytes with recombinant sFRP-1 (100 nM) significantly increased adiponectin (2.0-fold; P < 0.05), leptin (7-fold; P < 0.002), and TSH receptor mRNA (13-fold; P < 0.003) levels and enhanced Oil red-O staining in the cultures. Conclusions: These results support the concept that orbital adipogenesis is enhanced in GO and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process.

Original languageEnglish (US)
Pages (from-to)4730-4735
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume90
Issue number8
DOIs
StatePublished - Aug 2005

Fingerprint

Graves Ophthalmopathy
Adipogenesis
Gene Expression Profiling
Gene expression
Adipose Tissue
Genes
Tissue
Adiponectin
Oculomotor Muscles
Thyrotropin Receptors
Peroxisome Proliferator-Activated Receptors
Tissue Expansion
Leptin
Eye Diseases
frizzled related protein-1
Private Practice
Thyroid Diseases
Orbit
Surgery
Decompression

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Gene expression profiling of orbital adipose tissue from patients with Graves' ophthalmopathy : A potential role for secreted frizzled-related protein-1 in orbital adipogenesis. / Kumar, Seema; Leontovich, Alexey; Coenen, Michael J.; Bahn, Rebecca S.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 90, No. 8, 08.2005, p. 4730-4735.

Research output: Contribution to journalArticle

@article{38a4362dc43f40b3972dc33d84f0d5da,
title = "Gene expression profiling of orbital adipose tissue from patients with Graves' ophthalmopathy: A potential role for secreted frizzled-related protein-1 in orbital adipogenesis",
abstract = "Context: The signs and symptoms of Graves' ophthalmopathy (GO) result from inflammation and increased volume of the orbital adipose tissues and extraocular muscles. Objective: Our objective was to identify differentially regulated genes that may be involved in stimulating the orbital adipose tissue expansion seen in GO. Design: Gene expression profiling was used to compare genes expressed in orbital adipose tissues from GO patients and normal individuals. Setting: The study took place at a private practice tertiary referral center. Patients: Orbital adipose tissues were collected at transantral orbital decompression surgery from 20 euthyroid patients undergoing this procedure for severe GO and at early autopsy from eight normal individuals having no evidence of thyroid or ocular disease. Results: Of the 12,686 genes analyzed, 25 known genes were increased in expression (>4-fold) in GO orbital tissues, whereas 11 genes were decreased (>4-fold). Up-regulated genes, confirmed by quantitative RT-PCR, included secreted frizzled-related protein-1 (sFRP-1; 18.5-fold) and several adipocyte-related genes, including peroxisome proliferator activated receptor-γ(44.1-fold) and adiponectin (25-fold). Treatment in vitro of GO orbital preadipocytes with recombinant sFRP-1 (100 nM) significantly increased adiponectin (2.0-fold; P < 0.05), leptin (7-fold; P < 0.002), and TSH receptor mRNA (13-fold; P < 0.003) levels and enhanced Oil red-O staining in the cultures. Conclusions: These results support the concept that orbital adipogenesis is enhanced in GO and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process.",
author = "Seema Kumar and Alexey Leontovich and Coenen, {Michael J.} and Bahn, {Rebecca S.}",
year = "2005",
month = "8",
doi = "10.1210/jc.2004-2239",
language = "English (US)",
volume = "90",
pages = "4730--4735",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "8",

}

TY - JOUR

T1 - Gene expression profiling of orbital adipose tissue from patients with Graves' ophthalmopathy

T2 - A potential role for secreted frizzled-related protein-1 in orbital adipogenesis

AU - Kumar, Seema

AU - Leontovich, Alexey

AU - Coenen, Michael J.

AU - Bahn, Rebecca S.

PY - 2005/8

Y1 - 2005/8

N2 - Context: The signs and symptoms of Graves' ophthalmopathy (GO) result from inflammation and increased volume of the orbital adipose tissues and extraocular muscles. Objective: Our objective was to identify differentially regulated genes that may be involved in stimulating the orbital adipose tissue expansion seen in GO. Design: Gene expression profiling was used to compare genes expressed in orbital adipose tissues from GO patients and normal individuals. Setting: The study took place at a private practice tertiary referral center. Patients: Orbital adipose tissues were collected at transantral orbital decompression surgery from 20 euthyroid patients undergoing this procedure for severe GO and at early autopsy from eight normal individuals having no evidence of thyroid or ocular disease. Results: Of the 12,686 genes analyzed, 25 known genes were increased in expression (>4-fold) in GO orbital tissues, whereas 11 genes were decreased (>4-fold). Up-regulated genes, confirmed by quantitative RT-PCR, included secreted frizzled-related protein-1 (sFRP-1; 18.5-fold) and several adipocyte-related genes, including peroxisome proliferator activated receptor-γ(44.1-fold) and adiponectin (25-fold). Treatment in vitro of GO orbital preadipocytes with recombinant sFRP-1 (100 nM) significantly increased adiponectin (2.0-fold; P < 0.05), leptin (7-fold; P < 0.002), and TSH receptor mRNA (13-fold; P < 0.003) levels and enhanced Oil red-O staining in the cultures. Conclusions: These results support the concept that orbital adipogenesis is enhanced in GO and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process.

AB - Context: The signs and symptoms of Graves' ophthalmopathy (GO) result from inflammation and increased volume of the orbital adipose tissues and extraocular muscles. Objective: Our objective was to identify differentially regulated genes that may be involved in stimulating the orbital adipose tissue expansion seen in GO. Design: Gene expression profiling was used to compare genes expressed in orbital adipose tissues from GO patients and normal individuals. Setting: The study took place at a private practice tertiary referral center. Patients: Orbital adipose tissues were collected at transantral orbital decompression surgery from 20 euthyroid patients undergoing this procedure for severe GO and at early autopsy from eight normal individuals having no evidence of thyroid or ocular disease. Results: Of the 12,686 genes analyzed, 25 known genes were increased in expression (>4-fold) in GO orbital tissues, whereas 11 genes were decreased (>4-fold). Up-regulated genes, confirmed by quantitative RT-PCR, included secreted frizzled-related protein-1 (sFRP-1; 18.5-fold) and several adipocyte-related genes, including peroxisome proliferator activated receptor-γ(44.1-fold) and adiponectin (25-fold). Treatment in vitro of GO orbital preadipocytes with recombinant sFRP-1 (100 nM) significantly increased adiponectin (2.0-fold; P < 0.05), leptin (7-fold; P < 0.002), and TSH receptor mRNA (13-fold; P < 0.003) levels and enhanced Oil red-O staining in the cultures. Conclusions: These results support the concept that orbital adipogenesis is enhanced in GO and suggest that elevated levels of sFRP-1 in the GO orbit may be involved in stimulating this pathogenic process.

UR - http://www.scopus.com/inward/record.url?scp=23844476757&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=23844476757&partnerID=8YFLogxK

U2 - 10.1210/jc.2004-2239

DO - 10.1210/jc.2004-2239

M3 - Article

VL - 90

SP - 4730

EP - 4735

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 8

ER -