The mineralocorticoid receptor—an emerging player in metabolic syndrome?

Metabolic syndrome is a cluster of conditions that increase the risk of cardiovascular diseases, and comprises obesity, hypertension, impaired glucose metabolism and dyslipidaemia. It is well recognised that the mineralocorticoid receptor (MR) plays an important role in blood pressure regulation via its effect on salt and water retention in renal tubules, with hypertension being a key feature in primary aldosteronism patients with excess adrenal production of aldosterone, the primary ligand for MRs in the epithelial tissues. MRs are also expressed in a number of non-epithelial tissues including adipose tissue; in these tissues, glucocorticoids or cortisol can also activate MRs due to low levels of 11-beta-hydroxysteroid-dehydrogenase type 2 (11-βHSD2), the enzyme which inactivates cortisol. There is increasing evidence suggesting that over-activation of MRs plays a role in the pathophysiology of the other components of metabolic syndrome, promoting adiposity, inflammation and glucose intolerance, and that MR antagonists may confer beneficial effects on energy and substrate homeostasis and cardiometabolic diseases. This review discusses the advances in the literature shedding light on the MR as an emerging player in metabolic syndrome.