Endocrine Abstracts (2007) 13 P115

Glucocorticoid metabolic pathways in human orbital adipose tissue: a comparison with subcutaneous and omental depots

Claire Onyimba1, Iwona Bujalska2, Omar Durrani4, Joseph Abbott3, Pamela Khosla1, Areeb Moosavi4, Tristan Reuser4, Paul Stewart2, Jeremy Tomlinson2, Elizabeth Walker2 & Saaeha Rauz3

1Department of Endocrinology, Division of Medical Sciences and Academic Unit of Ophthalmology, Division of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom; 2Department of Endocrinology, Division of Medical Sciences, University of Birmingham, Birmingham, United Kingdom; 3Academic Unit of Ophthalmology, Division of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom; 4Birmingham and Midland Eye Centre, Birmingham, United Kingdom.

Orbital fat (OF) represents a highly specialised adipose tissue depot that occupies a confined space behind the eyeball known as the orbit. OF fills most of the orbital cavity providing support to the delicate structures that link the eye to the brain, and protects against sight-threatening mechanical and inflammatory trauma. Subcutaneous (SC) and omental (OM) adipose tissues are highly active endocrine organs, regulated in part by glucocorticoids (GCs). 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 mediating adipocyte hyperplasia and hypertrophy in the OM depot. In this study, we describe features of the GC metabolic pathways in normal human OF depot and compare it with SC and OM depots.

An automated histological characterisation technique (parameters: area, maximum diameter, perimeter) revealed that OF adipocytes in whole adipose tissue are significantly smaller compared with OM and SC adipocytes (P<0.001). Immunohistochemistry (IHC) demonstrated that OF tissue had a higher resident CD68+ cellular population compared to OM and SC fat (P<0.001), supported by real time RT-PCR analyses confirming increased CD68 mRNA expression (P<0.05) in this tissue. IHC revealed 11β-HSD1 expression in OF whole tissue whilst enzyme assays identified predominant 11β-HSD1 oxo-reductase activity in primary cultures of OF preadipocytes. However, 11β-HSD1 mRNA expression together with markers of late adipocyte differentiation (FABP4, G3PDH) were significantly lower in OF compared to SC and OM, whereas expression of H6PDH, GRα and CD68 mRNA were significantly higher in the OF tissue depot (P<0.05).

In summary, orbital adipocytes are smaller, less differentiated, and express low levels of 11β-HSD1 compared with SC and OM adipocytes, but higher GRα and H6PDH. The depot has a significantly larger CD68+ population. These characteristics define an orbital microenvironment that has a greater potential to respond to sight-threatening orbital inflammatory disease.