The mineralocorticoid system, cardiometabolic health and its interplay with adipose tissue

J Endocrinol. 2024 Oct 16;263(2):e240119. doi: 10.1530/JOE-24-0119. Print 2024 Nov 1.

Abstract

The mineralocorticoid system, comprising the renin-angiotensin-aldosterone system (RAAS) and associated receptors, is traditionally viewed as a regulator of sodium and fluid balance and blood pressure (BP), with the main mineralocorticoid hormone aldosterone acting via the mineralocorticoid receptor (MR) in distal renal tubules. Over the past few decades, there has been a wider understanding of the role of the mineralocorticoid system in regulating both classical BP-dependent and non-BP-dependent systemic effects. Mounting evidence indicates the novel role of the mineralocorticoid system in cardiometabolic health, with excess mineralocorticoid system activity being associated with adiposity, diabetes, insulin resistance and cardiovascular diseases independent of its effect on BP, and RAAS blockade and MR antagonists offering protection against cardiometabolic dysfunction. The metabolic manifestations of mineralocorticoid system overactivation are mainly mediated by their interactions with adipose tissue, which orchestrates energy, lipids, and glucose homeostasis via effects on the functions of brown and white adipocytes and immune cells. Adipose tissue can, in turn, influence mineralocorticoid system activity by harboring its own RAAS system and by releasing mineralocorticoid-secretory factors/adipokines, resulting in further progression of cardiometabolic dysfunction. This article discusses the interplay between the mineralocorticoid system and adipose tissue in the pathophysiology of cardiometabolic diseases.

Keywords: adipose tissue; aldosterone; angiotensin; cardiometabolic health; metabolic syndrome; metabolism; mineralocorticoid; mineralocorticoid receptor.

Publication types

  • Review

MeSH terms

  • Adipose Tissue* / metabolism
  • Animals
  • Cardiovascular Diseases* / etiology
  • Cardiovascular Diseases* / metabolism
  • Humans
  • Insulin Resistance / physiology
  • Mineralocorticoids* / metabolism
  • Receptors, Mineralocorticoid* / metabolism
  • Renin-Angiotensin System* / physiology

Substances

  • Mineralocorticoids
  • Receptors, Mineralocorticoid