Endocrine Abstracts

Patients with Cushing's syndrome develop florid, but reversible central obesity. However, circulating cortisol levels are not elevated in simple obesity. Within human adipose tissue, the enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is highly expressed and converts inactive glucocorticoid, cortisone to active cortisol. Rodents over-expressing 11beta-HSD1 in adipocytes develop central obesity exclusively as a result of increased adipocyte size. Whilst it has been speculated that over-expression of this enzyme, leading to increased adipose tissue cortisol levels, may be a key process in the pathogenesis of human obesity, this has not been convincingly demonstrated in clinical studies.
We have performed a histomorphometric analysis of paired omental and subcutaneous fat biopsies from 10 consecutive patients undergoing elective abdominal surgery for benign conditions (BMI 24.2kg/m² [21.2-39.7], median and range). In addition, we have used real-time PCR to determine adipocyte specific expression of 11beta-HSD1.
Subcutaneous adipocyte diameter was greater than omental diameter in all patients (119.5 plus/minus 4.1 vs. 90.3 plus/minus 4.5microns mean plus/minus SE, p=0.0001). In both subcutaneous and omental samples, adipocyte size increased with body mass index (Omental: R=0.66, p=0.04; Subcutaneous R=0.66, p=0.04). 11beta-HSD1 expression in adipocytes was similar in subcutaneous and omental samples (dct 13.0 plus/minus 0.3 vs. 12.6 plus/minus 0.7, p=0.65). Furthermore, there was no correlation between 11beta-HSD1 expression and BMI (Omental: R=0.30, p=0.45; Subcutaneous R=-0.14, p=0.72), nor between 11b-HSD1 expression and adipocyte size (Omental: R=-0.39, p=0.3; Subcutaneous R=0.12, p=0.75).
We have highlighted the difference in histomorphometry between paired subcutaneous and omental adipose tissue biopsies. Control and regulation of adipocyte size is a complex process and is unlikely to be dependant upon a single factor, or the expression of a single gene in isolation. Whilst glucocorticoid excess has a profound impact upon adipose tissue biology, 11beta-HSD1 expression alone is not able to predict adipocyte size in human adipose tissue.