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Characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat

Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that activates cortisol from cortisone has been postulated as a fundamental mechanism underlying th...

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Autores principales: Bujalska, Iwona J, Durrani, Omar M, Abbott, Joseph, Onyimba, Claire U, Khosla, Pamela, Moosavi, Areeb H, Reuser, Tristan T Q, Stewart, Paul M, Tomlinson, Jeremy W, Walker, Elizabeth A, Rauz, Saaeha
Formato: Texto
Lenguaje:English
Publicado: Society for Endocrinology 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994563/
https://www.ncbi.nlm.nih.gov/pubmed/17283228
http://dx.doi.org/10.1677/JOE-06-0042
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author Bujalska, Iwona J
Durrani, Omar M
Abbott, Joseph
Onyimba, Claire U
Khosla, Pamela
Moosavi, Areeb H
Reuser, Tristan T Q
Stewart, Paul M
Tomlinson, Jeremy W
Walker, Elizabeth A
Rauz, Saaeha
author_facet Bujalska, Iwona J
Durrani, Omar M
Abbott, Joseph
Onyimba, Claire U
Khosla, Pamela
Moosavi, Areeb H
Reuser, Tristan T Q
Stewart, Paul M
Tomlinson, Jeremy W
Walker, Elizabeth A
Rauz, Saaeha
author_sort Bujalska, Iwona J
collection PubMed
description Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that activates cortisol from cortisone has been postulated as a fundamental mechanism underlying the metabolic syndrome mediating adipocyte hyperplasia and hypertrophy in the omental (OM) depot. Orbital adipose tissue (OF) is the site of intense inflammation and tissue remodelling in several orbital inflammatory disease states. In this study, we describe features of the GC metabolic pathways in normal human OF depot and compare it with subcutaneous (SC) and OM depots. Using an automated histological characterisation technique, OF adipocytes were found to be significantly smaller (parameters: area, maximum diameter and perimeter) than OM and SC adipocytes (P<0·001). Although immunohistochemical analyses demonstrated resident CD68(+) cells in all three whole tissue adipose depots, OF CD68 mRNA and protein expression exceeded that of OM and SC (mRNA, P<0·05; protein, P<0·001). In addition, there was higher expression of glucocorticoid receptor (GR)α mRNA in the OF whole tissue depot (P<0·05). Conversely, 11β-HSD1 mRNA together with the markers of late adipocyte differentiation (FABP4 and G3PDH) were significantly lower in OF. Primary cultures of OF preadipocytes demonstrated predominant 11β-HSD1 oxo-reductase activity with minimal dehydrogenase activity. Orbital adipocytes are smaller, less differentiated, and express low levels of 11β-HSD1 but abundant GRα compared with SC and OM. OF harbours a large CD68(+) population. These characteristics define an orbital microenvironment that has the potential to respond to sight-threatening orbital inflammatory disease.
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spelling pubmed-19945632009-01-27 Characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat Bujalska, Iwona J Durrani, Omar M Abbott, Joseph Onyimba, Claire U Khosla, Pamela Moosavi, Areeb H Reuser, Tristan T Q Stewart, Paul M Tomlinson, Jeremy W Walker, Elizabeth A Rauz, Saaeha J Endocrinol Regular Papers Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that activates cortisol from cortisone has been postulated as a fundamental mechanism underlying the metabolic syndrome mediating adipocyte hyperplasia and hypertrophy in the omental (OM) depot. Orbital adipose tissue (OF) is the site of intense inflammation and tissue remodelling in several orbital inflammatory disease states. In this study, we describe features of the GC metabolic pathways in normal human OF depot and compare it with subcutaneous (SC) and OM depots. Using an automated histological characterisation technique, OF adipocytes were found to be significantly smaller (parameters: area, maximum diameter and perimeter) than OM and SC adipocytes (P<0·001). Although immunohistochemical analyses demonstrated resident CD68(+) cells in all three whole tissue adipose depots, OF CD68 mRNA and protein expression exceeded that of OM and SC (mRNA, P<0·05; protein, P<0·001). In addition, there was higher expression of glucocorticoid receptor (GR)α mRNA in the OF whole tissue depot (P<0·05). Conversely, 11β-HSD1 mRNA together with the markers of late adipocyte differentiation (FABP4 and G3PDH) were significantly lower in OF. Primary cultures of OF preadipocytes demonstrated predominant 11β-HSD1 oxo-reductase activity with minimal dehydrogenase activity. Orbital adipocytes are smaller, less differentiated, and express low levels of 11β-HSD1 but abundant GRα compared with SC and OM. OF harbours a large CD68(+) population. These characteristics define an orbital microenvironment that has the potential to respond to sight-threatening orbital inflammatory disease. Society for Endocrinology 2007-02 /pmc/articles/PMC1994563/ /pubmed/17283228 http://dx.doi.org/10.1677/JOE-06-0042 Text en © 2007 Society for Endocrinology http://www.endocrinology.org/journals/reuselicence/ This is an Open Access article distributed under the terms of the Society for Endocrinology's Re-use Licence (http://www.endocrinology.org/journals/reuselicence/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Regular Papers
Bujalska, Iwona J
Durrani, Omar M
Abbott, Joseph
Onyimba, Claire U
Khosla, Pamela
Moosavi, Areeb H
Reuser, Tristan T Q
Stewart, Paul M
Tomlinson, Jeremy W
Walker, Elizabeth A
Rauz, Saaeha
Characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat
title Characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat
title_full Characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat
title_fullStr Characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat
title_full_unstemmed Characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat
title_short Characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat
title_sort characterisation of 11β-hydroxysteroid dehydrogenase 1 in human orbital adipose tissue: a comparison with subcutaneous and omental fat
topic Regular Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1994563/
https://www.ncbi.nlm.nih.gov/pubmed/17283228
http://dx.doi.org/10.1677/JOE-06-0042
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