The pathophysiology of cardio-metabolic diseases involves a delicate interplay between biological and environmental factors regulating energy homeostasis, water and electrolyte balance, as well as inflammation and oxidative stress in critical organs for cardio-metabolic health.

In this context, several studies clearly demonstrated a specific role of extra-renal mineralocorticoid receptors (MR) in controlling endothelial function, vascular tone, adipose tissue differentiation and inflammation, and heart physiology. In preclinical models, abnormal activation of MR in the vascular endothelial cells and in adipocyte favors the occurrence of several components of the metabolic syndrome, such as hypertension, obesity, and glucose intolerance. Moreover, it is well known that high circulating levels of aldosterone are associated with obesity and metabolic syndrome in humans, suggesting that altered activation of the MR in extra-renal tissues leads to important metabolic alterations. In this context, MR antagonists represent a promising approach to tackle cardiovascular and metabolic disorders occurring in the metabolic syndrome, even if there is still an important gap of knowledge about the metabolic effects of MR antagonists in clinical settings. This talk will discuss the complex interplay between the mineralocorticoid system, adipose tissue and endothelial cells and its role in the pathophysiology of cardio-metabolic diseases.