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Integrative Biology

Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women

Abstract

Background:

Black women have lower visceral adipose tissue (VAT) but are less insulin sensitive than white women; the mechanisms responsible are unknown.

Objective:

The study aimed to test the hypothesis that variation in subcutaneous adipose tissue (SAT) sensitivity to glucocorticoids might underlie these differences.

Methods:

Body fatness (dual energy X-ray absorptiometry) and distribution (computerized tomography), insulin sensitivity (SI, intravenous and oral glucose tolerance tests), and expression of 11β-hydroxysteroid dehydrogenase-1 (11HSD1), hexose-6-phosphate dehydrogenase and glucocorticoid receptor-α (GRα), as well as genes involved in adipogenesis and inflammation were measured in abdominal deep SAT, superficial SAT and gluteal SAT (GLUT) depots of 56 normal-weight or obese black and white premenopausal South African (SA) women. We used a combination of univariate and multivariate statistics to evaluate ethnic-specific patterns in adipose gene expression and related body composition and insulin sensitivity measures.

Results:

Although 11HSD1 activity and mRNA did not differ by ethnicity, GRα mRNA levels were significantly lower in SAT of black compared with white women, particularly in the GLUT depot (0.52±0.21 vs 0.91±0.26 AU, respectively, P<0.01). In black women, lower SAT GRα mRNA levels were associated with increased inflammatory gene transcript levels and abdominal SAT area, and reduced adipogenic gene transcript levels, VAT/SAT ratio and SI. Abdominal SAT 11HSD1 activity associated with increased VAT area and decreased SI in white, but not in black women.

Conclusions:

In black SA women, downregulation of GRα mRNA levels with obesity and reduced insulin sensitivity, possibly via increased SAT inflammation, is associated with reduced VAT accumulation.

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Acknowledgements

We thank the research volunteers for their participation in this study. J Bergman and N Fenton of Symington Radiology are thanked for performing the computerized tomography scans and L Bewerunge is thanked for performing the dual-energy X-ray absorptiometry scans. S West is acknowledged for her clinical support. This study was funded by the South African Medical Research Council, the International Atomic Energy Agency, the National Research Foundation of South Africa and Royal Society SA-UK Science Networks Program, the University of Cape Town, the British Heart Foundation, the Welcome Trust, the United States Department of Veterans Affairs and the Swedish Heart and Lung Foundation.

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Correspondence to J H Goedecke.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Goedecke, J., Chorell, E., Livingstone, D. et al. Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women. Int J Obes 39, 303–311 (2015). https://doi.org/10.1038/ijo.2014.94

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