Mineralocorticoid receptors in non-alcoholic fatty liver disease

Br J Pharmacol. 2022 Jul;179(13):3165-3177. doi: 10.1111/bph.15784. Epub 2022 Feb 4.

Abstract

Liver diseases are the fourth common death in Europe responsible for about 2 million death per year worldwide. Among the known detrimental causes for liver dysfunction are virus infections, intoxications and obesity. The mineralocorticoid receptor (MR) is a ligand-dependent transcription factor activated by aldosterone or glucocorticoids but also by pathological milieu factors. Canonical actions of the MR take place in epithelial cells of kidney, colon and sweat glands and contribute to sodium reabsorption, potassium secretion and extracellular volume homeostasis. The non-canonical functions can be initiated by inflammation or an altered micro-milieu leading to fibrosis, hypertrophy and remodelling in various tissues. This narrative review summarizes the evidence regarding the role of MR in portal hypertension, non-alcoholic fatty liver disease, liver fibrosis and cirrhosis, demonstrating that inhibition of the MR in vivo seems to be beneficial for liver function and not just for volume regulation. Unfortunately, the underlying molecular mechanisms are still not completely understood. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.

Keywords: NAFL; aldosterone; cirrhosis; hepatic stellate cell; hepatocytes; liver; mineralocorticoid receptor.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone
  • Fibrosis
  • Homeostasis
  • Humans
  • Liver Cirrhosis
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Receptors, Mineralocorticoid* / metabolism

Substances

  • Receptors, Mineralocorticoid
  • Aldosterone