Cellular mechanisms of MR regulation of adipose tissue physiology and pathophysiology

Abstract

In addition to the well-documented expression and activity of the mineralocorticoid receptor (MR) in the kidney, in the last decade research on MR has also revealed its important role in regulating functions of extrarenal tissues, including adipose tissue, where MR is involved in adipocyte fundamental processes such as differentiation, autophagy and adipokine secretion. MR expression is increased in adipose tissue of murine models of obesity and in obese human subjects, suggesting that over-activation of the mineralocorticoid signaling leads to dysfunctional adipocyte and associated metabolic disorders. Notably, pharmacological blockade of MR prevents metabolic dysfunctions observed in obese mice and suggests a potential therapeutic use of MR antagonists in the treatment of obesity and metabolic syndrome. However, the molecular pathways affected by MR blockade have been poorly investigated. This review summarizes the functions of MR in the adipocyte, discusses potential signaling pathways mediating MR action, and describes post-translational modifications regulating its activity.

Molecular mechanisms underlying metabolic syndrome: the expanding role of the adipocyte

“…In addition, MR antagonists have well-established beneficial effects at the vascular and cardiac levels, which supports the notion that MR antagonists act at a multisystemic level, reducing blood pressure, tissue fibrosis, oxidative stress, insulin resistance, and adipose mass expansion, with potential global protective effects on MetS (108). Indirect evidence emerges from clinical studies that demonstrate that the prevalence of MetS is higher in primary aldosteronism than in essential hypertension (109), mostly for a detrimental effect of aldosterone excess on glucose metabolism and on adipose tissue physiology (110,111).…”

Comment on “mineralocorticoid antagonism enhances brown adipose tissue function in humans: A randomized placebo‐controlled cross‐over study”

“…Spiro enhanced BAT thermogenic activity on cooling or in response to a mixed meal, with a parallel increase in postprandial fat oxidation and reduction in lipid synthesis, indicating that MR blockade promotes energy dissipation as heat and leads to less availability of energy for storage of nutrients, in accordance with the complex regulation of adipose tissue by MR …”

Impact of MR on mature adipocytes in high-fat/high-sucrose diet-induced obesity

“…The mineralocorticoid receptor (MR) is a member of the steroid receptor family of ligand activated transcription factors. MR is expressed in several tissues, including the kidney, heart, colon, brain and adipose tissue (Armani et al 2015). In the kidney, its activation leads to the expression of ENaC or Na/K ATPase resulting in the reabsorption of sodium to maintain a normal salt concentration in the body.…”