Cortisol metabolism after weight loss: associations with 11 β‐HSD type 1 and markers of obesity in women

Abstract

Increased glucocorticoid metabolite excretion and enhanced expression and activity of 11β-hydroxysteroid dehydrogenase type 1 in adipose tissue are closely correlated with obesity and its detrimental consequences. Weight loss ameliorates the latter. The aim of this study was to explore whether increased glucocorticoid exposure in obesity is improved with substantial weight loss and thus is a consequence rather than a cause of obesity. A prospective cohort study in 31 women. 11β-HSD type 1 expression and activity, urinary glucocorticoid metabolite excretion, body composition including regional adipose tissue depots and insulin resistance by HOMA-IR before and 2years after gastric bypass surgery. After weight loss, excretion of cortisol and cortisone metabolites decreased. Both cortisol and cortisone metabolite excretion correlated with central obesity, where the intraabdominal fat depot showed the strongest association. Cortisol metabolites correlated with 11β-HSD type 1 activity in abdominal subcutaneous adipose tissue. The ratio of cortisol to cortisone metabolites [(5α-tetrahydrocortisol (5αTHF)+tetrahydrocortisol (THF)+α-cortol)/(tetrahydrocortisone (THE)+α-cortolone)] and the ratio of 5α-THF/THF both decreased after stable weight loss, reflecting a downregulation of the net activities of 11β-HSD type 1 and 5α-reductase. Long-term weight loss in women is not only followed by reduced glucocorticoid production, but also favourably decreases the global and tissue-specific activity of the cortisol-activating enzyme 11 β-HSD type 1, possibly contributing to the health benefits of bariatric surgery.