Mineralocorticoid receptor in adipocytes and macrophages: A promising target to fight metabolic syndrome

• The MR is expressed and functional in several tissues controlling metabolic homeostasis.
• MR antagonism in murine models of metabolic syndrome displays beneficial metabolic effects.
• Metabolic effects of MR antagonists in human subjects are still unclear.
• Adipocyte and macrophage MR may play a major role in controlling metabolic homeostasis.

Aldosterone is the primary ligand for the mineralocorticoid receptor (MR) and has been considered long time a “renal” hormone, acting at this site as a key regulator of plasma volume, electrolyte homeostasis and blood pressure. A new exciting era of MR biology began with the identification of MR in different non-epithelial tissues such as brain, heart, vessels, macrophages/monocytes, and adipose tissue. The distribution of MR in such a wide range of tissues has suggested novel and unexpected roles for MR, for example in energy metabolism and inflammation. An increasing body of evidence suggests a detrimental effect of aldosterone excess on the development of metabolic alterations. Disturbances in glucose metabolism due to inappropriate activation of MR are frequently observed in patients with primary aldosteronism as well as in obese subjects. MR antagonists have beneficial effects on glucose tolerance and metabolic parameters in experimental animals, whereas their role in humans remains unclear. The aim of this review is to discuss the pathophysiology of MR activation in experimental models, particularly at the level of adipocytes and macrophages, to discuss novel and sometimes contrasting insights from emerging studies, and to highlight deficiencies in the field.