Expression of 11β-hydroxysteroid dehydrogenase type 1 in visceral and subcutaneous adipose tissues of patients with polycystic ovary syndrome is associated with adiposity

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance (IR) and central obesity. The impact of adipose tissue cortisol reactivation by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) on markers of obesity and IR was assessed in PCOS patients. Eighty-five PCOS patients and 43 controls were enrolled for subcutaneous adipose tissue biopsy; 25/85 patients and 29/43 controls underwent also visceral adipose tissue biopsy. HSD11B1 gene expression and expression of lipid metabolism genes were measured in subcutaneous and visceral adipose tissues. Anthropometric and biochemical markers of IR and PCOS were also assessed. HSD11B1 expression in visceral and subcutaneous adipose tissue was increased in PCOS patients compared to controls (p<0.05). After BMI adjustment, the difference was no longer significant. In PCOS patients, visceral HSD11B1 expression correlated positively with waist circumference (p=0.001), BMI (p=0.002), plasma insulin (p<0.05), systolic blood pressure (p=0.003), and lipoprotein lipase (LPL), hormone-sensitive lipase (LIPE) and peroxisome-proliferator activated receptor γ gene expression. Subcutaneous HSD11B1 expression correlated positively with BMI, waist circumference (p<0.001 for both) and HOMA-IR (p=0.003), and negatively with LPL, LIPE, adiponectin and glucose transporter GLUT4 gene expression. HSD11B1 expression in both depots showed a negative correlation with plasma HDL-cholesterol (p<0.03) and a positive one with C-reactive protein (p<0.001). In multiple regression analysis, HSD11B1 expression in visceral adipose tissue was most prominently associated with waist circumference, and that in subcutaneous adipose tissue with BMI (p<0.001 for both). Our results show that PCOS is not associated with increased HSD11B1 expression once adiposity is controlled for. Increased expression of this gene correlates with markers of adiposity and predicts IR and an unfavorable metabolic profile, independently of PCOS.