Hypoxia and extra-cellular matrix gene expression in adipose tissue associates with reduced insulin sensitivity in black South African women.

Black South African women are more insulin resistant and have increased gluteal subcutaneous adipose tissue hypertrophy than white South African women. We tested the hypothesis that adipose tissue hypoxia and extracellular matrix gene expression in gluteal and abdominal subcutaneous adipose tissue is higher in black than white women, and associates with reduced insulin sensitivity in black women. Insulin sensitivity (frequently sampled intravenous glucose tolerance test), gluteal and abdominal subcutaneous adipose tissue mRNA levels of hypoxia- and extracellular matrix-related genes were measured in normal-weight and obese premenopausal black (n = 30) and white (n = 26) South African women at baseline, and in black women, at 5-year follow-up (n = 10). Compared to obese white women, obese black women had higher expression of hypoxia inducible factor 1, collagen Vα1 and collagen VIα1 and reduced vascular endothelial growth factor-α expression in gluteal (p < 0.05) but not abdominal subcutaneous adipose tissue depots. Independent of age and body fatness, gluteal expression of hypoxia inducible factor 1 (r = -0.55; p = 0.01), collagen Vα1 (r = -0.41; p = 0.05) and collagen VIα1 (r = -0.47; p = 0.03) correlated with reduced insulin sensitivity in black women only. Over a 5-year follow-up, changes in gluteal hypoxia inducible factor 1 (r = 0.77; p = 0.01) collagen Vα1 (r = 0.71; p = 0.02) and collagen VIα1 (r = 0.81; p < 0.01) expression correlated positively with the change in fasting insulin concentrations in black women. Compared to their white counterparts, black women expressed higher levels of genes associated with hypoxia and collagen deposition, and the associations between these genes and insulin sensitivity differed by ethnicity. We thus propose that insulin resistance in black women may be related to higher extracellular matrix and hypoxia gene expression.