Glucocorticoid metabolism within superficial subcutaneous rather than visceral adipose tissue is associated with features of the metabolic syndrome in South African women

Abstract

Glucocorticoid hyperactivity in adipose tissue, due to up-regulation of local glucocorticoid reactivation by 11beta-hydroxysteroid dehydrogenase-1 (11HSD1) or of glucocorticoid receptors (GR), may underpin susceptibility to the metabolic syndrome. This hypothesis has been tested extensively in subcutaneous adipose tissue (SAT) but inadequately in visceral adipose tissue (VAT). The aim of the study was therefore to examine expression of 11HSD1, GRalpha and hexose-6-phosphate dehydrogenase (H6PDH), which supplies cofactor for 11HSD1, in abdominal adipose tissue compartments and to characterize their relation to metabolic syndrome parameters. A cross-sectional study including 26 premenopausal South African women. Biopsies were taken for measurement of mRNA levels by real-time polymerase chain reaction (RT-PCR) and 11HSD1 activity from VAT, and deep and superficial SAT compartments during elective surgery. Prior to surgery, blood pressure, blood lipid profile, body composition [by dual X-ray absorptiometry (DEXA) scan], body fat distribution [by computed tomography (CT) scan], and glucose tolerance were determined. 11HSD1 activity (P < 0.01) was higher in VAT than SAT, but 11HSD1 and GRalpha mRNA levels were not statistically different between compartments. 11HSD1 mRNA levels in superficial SAT correlated with VAT volume (R = 0.57, P < 0.01), insulin sensitivity calculated from the oral glucose tolerance test (OGTT) (R = -0.52, P < 0.016) and blood pressure (R = 0.48, P < 0.016). Apart from a correlation between deep SAT 11HSD1 activity and blood pressure (R = 0.72, P < 0.01), glucocorticoid action in deep SAT and VAT depots was not significantly associated with any metabolic syndrome parameters. Increased capacity for glucocorticoid regeneration in superficial SAT but not VAT is associated with visceral adiposity and other features of the metabolic syndrome in women.