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

Abstract

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.

Expression of genes related to glucocorticoid action in human subcutaneous and omental adipose tissue

“…Messenger RNA levels of this receptor were found to be higher in omental than in subcutaneous adipose tissue in some, but not all, studies [6,10,[19][20][21]. Negative associations between GR␣ mRNA expression and adiposity measures were previously reported [6,19].…”

Association of serum cortisol levels with parameters of metabolic syndrome in men and women

“…Previous studies suggested that increased serum cortisol level in men is mainly mediated through 11b-hydroxysteroid dehydrogenase type 1 (11b-HSD1) activity [24,25]. 11b-HSD1is a bidirectional enzyme, located in the abdominal fat mass and omental subcutaneous tissue, and mediates the conversion of cortisone to cortisol [26,27] thermore there are gender di erences in 11b-HSD1 activity, which is greater in men [20], and 5a-reductase activity, which is greater in women [28]. is di erence in enzyme activity may result in an increase in serum cortisol levels in men and would alter its degree of correlation with parameters associated with metabolic syndrome.…”

Depot-specific characteristics of adipose tissue-derived stromal cells in thyroid-associated orbitopathy

“…Ilankovan and Soames22 found comparable relative volumes of collagen and endothelial cells, as well as the density of mast cells between orbital and buccal fat, which were significantly different from those in subcutaneous fat from non-TAO patients. Another study found that adipocytes from the orbit were significantly smaller in area, maximum diameter and perimeter than adipocytes from omental and subcutaneous adipose tissues in non-obese (BMI <25 kg/m 2 ) patients 23. The authors also showed higher expression of CD68 and glucocorticoid receptor alpha in orbital adipocytes than in omental and subcutaneous adipocytes.…”