Glucocorticoid receptor gene expression in adipose tissue and associated metabolic risk in black and white South African women.
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.
1] Non-Communicable Disease Research Unit, South African Medical Research Council, Cape Town, South Africa [2] UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, Cape Town, South Africa.
J H
JH
Goedecke
Department of Public Health and Clinical Medicine, Umeå University, Umea, Sweden.
E
E
Chorell
Endocrinology Unit, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
D E W
DE
Livingstone
Endocrinology Unit, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
R H
RH
Stimson
Divison of Surgery, Department of Plastic Surgery, University of Cape Town, Cape Town, South Africa.
P
P
Hayes
Divison of Surgery, Department of Plastic Surgery, University of Cape Town, Cape Town, South Africa.
K
K
Adams
Division of Diabetes and Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
J A
JA
Dave
UCT/MRC Research Unit for Exercise Science and Sports Medicine, Department of Human Biology, Cape Town, South Africa.
H
H
Victor
Division of Diabetes and Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
N S
NS
Levitt
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA.
S E
SE
Kahn
Endocrinology Unit, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
J R
JR
Seckl
Endocrinology Unit, University/British Heart Foundation Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
B R
BR
Walker
Department of Public Health and Clinical Medicine, Umeå University, Umea, Sweden.
T
T
Olsson
D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D015502:Absorptiometry, Photon; D000328:Adult; D044383:Black People; D001823:Body Composition / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000208:ethnology / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013019:South Africa / Q000453:epidemiology; D050151:Subcutaneous Fat / Q000378:metabolism*; D044465:White People
D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D042842:11-beta-Hydroxysteroid Dehydrogenases