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

Int J Obes (Lond). 2015 Feb;39(2):303-11. doi: 10.1038/ijo.2014.94. Epub 2014 May 20.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenases / genetics
  • 11-beta-Hydroxysteroid Dehydrogenases / metabolism*
  • Absorptiometry, Photon
  • Adult
  • Black People*
  • Body Composition / genetics
  • Cross-Sectional Studies
  • Female
  • Glucose Tolerance Test
  • Humans
  • Intra-Abdominal Fat / metabolism*
  • Metabolic Syndrome / ethnology
  • Metabolic Syndrome / genetics
  • Metabolic Syndrome / metabolism*
  • Receptors, Glucocorticoid / metabolism*
  • South Africa / epidemiology
  • Subcutaneous Fat / metabolism*
  • White People*

Substances

  • Receptors, Glucocorticoid
  • glucocorticoid receptor alpha
  • 11-beta-Hydroxysteroid Dehydrogenases