Introduction: Increased capacity for glucocorticoid regeneration in subcutaneous adipose tissue (SAT) by 11β-hydroxysteroid dehydrogenase-1 (11HSD1) is associated with obesity and associated risk factors. We hypothesised that down-regulation of SAT 11HSD1 and/or glucocorticoid receptor-α (GRα) may explain differences in body fat distribution and metabolic risk between black and white women. The study aimed to compare the expression of 11HSD1 and glucocorticoid receptor-α (GRα), and glucocorticoid-responsive genes in gluteal SAT depots, and determine their relationships with body composition and metabolic risk factors in South African women.
Methods: Body fatness (DXA) and distribution (computerized tomography), insulin sensitivity (SI, intravenous glucose tolerance test) and the expression of 11HSD1, GRα, PPARγ, adiponectin, CD68 and TNFα were measured in gluteal SAT of 56 normal-weight and obese black and white premenopausal South African women.
Results: 11HSD1 expression was increased with obesity in both black and white women (P<0.001), but did not differ by ethnicity. In contrast, GRα mRNA levels were significantly lower in both normal weight and obese black compared to white women (0.86±0.25 vs 1.31±0.65 AU and 0.52±0.21 vs 0.91±0.26 AU, respectively, P<0.01). Lower GRα expression in black women was associated with increased CD68 (r=−0.64, P<0.001) and TNFα (r=−0.39, P<0.01), reduced PPARγ (r=0.84, P<0.001) and adiponectin mRNA levels (r=0.47, P<0.001), as well as increased fat mass (r=−0.61, P=0.001) and serum triglycerides (r=−0.43, P=0.022), and reduced HDL-cholesterol (r=0.48, P=0.010) and SI (r=0.47, P=0.016).
Conclusions: Expression of GRα is downregulated in gluteal SAT of black South African women, and associates with reduced adipogenic capacity and increased metabolic risk factors.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.