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

Bujalska IJ, Durrani OM, Abbott J, Onyimba CU, Khosla P, Moosavi AH, Reuser TT, Stewart PM, Tomlinson JW, Walker EA, Rauz S - J. Endocrinol. (2007)

Bottom Line: 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 x 001).Primary cultures of OF preadipocytes demonstrated predominant 11beta-HSD1 oxo-reductase activity with minimal dehydrogenase activity.Orbital adipocytes are smaller, less differentiated, and express low levels of 11beta-HSD1 but abundant GRalpha compared with SC and OM.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Division of Medical Sciences, University of Birmingham, Birmingham, UK.

ABSTRACT
Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-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 x 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 x 05; protein, P<0 x 001). In addition, there was higher expression of glucocorticoid receptor (GR)alpha mRNA in the OF whole tissue depot (P<0 x 05). Conversely, 11beta-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 11beta-HSD1 oxo-reductase activity with minimal dehydrogenase activity. Orbital adipocytes are smaller, less differentiated, and express low levels of 11beta-HSD1 but abundant GRalpha 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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Whole adipose tissue real time RT-PCR analyses showed significantly higher expression of 11β-HSD1 and H6PDH mRNA in SC and OM when compared with OF. Conversely, highest expression of GRα mRNA in OF when compared with SC and OM is seen (A). FABP4, G3PDH mRNA expression (markers of late adipocyte differentiation) were significantly lower in OF (B). Results are expressed as fold-change when compared with orbital fat; dCt are shown in tables below (*P<0·05; †P<0·001).
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fig5: Whole adipose tissue real time RT-PCR analyses showed significantly higher expression of 11β-HSD1 and H6PDH mRNA in SC and OM when compared with OF. Conversely, highest expression of GRα mRNA in OF when compared with SC and OM is seen (A). FABP4, G3PDH mRNA expression (markers of late adipocyte differentiation) were significantly lower in OF (B). Results are expressed as fold-change when compared with orbital fat; dCt are shown in tables below (*P<0·05; †P<0·001).

Mentions: 11β-HSD1 mRNA was expressed within OF tissue, although quantitative real-time PCR analyses across the three whole adipose tissue depots revealed lowest levels of expression in OF when compared with SC and OM adipose depots (OF=1; SC=8·1, P<0·001; OM=10<0·001 (fold-change when compared with OF); Fig. 5A). Nevertheless, these data reflect our 11β-HSD1 oxo-reductase activity data detailed earlier.


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

Bujalska IJ, Durrani OM, Abbott J, Onyimba CU, Khosla P, Moosavi AH, Reuser TT, Stewart PM, Tomlinson JW, Walker EA, Rauz S - J. Endocrinol. (2007)

Whole adipose tissue real time RT-PCR analyses showed significantly higher expression of 11β-HSD1 and H6PDH mRNA in SC and OM when compared with OF. Conversely, highest expression of GRα mRNA in OF when compared with SC and OM is seen (A). FABP4, G3PDH mRNA expression (markers of late adipocyte differentiation) were significantly lower in OF (B). Results are expressed as fold-change when compared with orbital fat; dCt are shown in tables below (*P<0·05; †P<0·001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC1994563&req=5

fig5: Whole adipose tissue real time RT-PCR analyses showed significantly higher expression of 11β-HSD1 and H6PDH mRNA in SC and OM when compared with OF. Conversely, highest expression of GRα mRNA in OF when compared with SC and OM is seen (A). FABP4, G3PDH mRNA expression (markers of late adipocyte differentiation) were significantly lower in OF (B). Results are expressed as fold-change when compared with orbital fat; dCt are shown in tables below (*P<0·05; †P<0·001).
Mentions: 11β-HSD1 mRNA was expressed within OF tissue, although quantitative real-time PCR analyses across the three whole adipose tissue depots revealed lowest levels of expression in OF when compared with SC and OM adipose depots (OF=1; SC=8·1, P<0·001; OM=10<0·001 (fold-change when compared with OF); Fig. 5A). Nevertheless, these data reflect our 11β-HSD1 oxo-reductase activity data detailed earlier.

Bottom Line: 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 x 001).Primary cultures of OF preadipocytes demonstrated predominant 11beta-HSD1 oxo-reductase activity with minimal dehydrogenase activity.Orbital adipocytes are smaller, less differentiated, and express low levels of 11beta-HSD1 but abundant GRalpha compared with SC and OM.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Division of Medical Sciences, University of Birmingham, Birmingham, UK.

ABSTRACT
Glucocorticoids (GCs) have a profound effect on adipose biology increasing tissue mass causing central obesity. The pre-receptor regulation of GCs by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-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 x 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 x 05; protein, P<0 x 001). In addition, there was higher expression of glucocorticoid receptor (GR)alpha mRNA in the OF whole tissue depot (P<0 x 05). Conversely, 11beta-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 11beta-HSD1 oxo-reductase activity with minimal dehydrogenase activity. Orbital adipocytes are smaller, less differentiated, and express low levels of 11beta-HSD1 but abundant GRalpha 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.

Show MeSH
Related in: MedlinePlus