Beyond the X Factor: Relevance of Sex Hormones in NAFLD Pathophysiology

Cells. 2021 Sep 21;10(9):2502. doi: 10.3390/cells10092502.

Abstract

Non-alcoholic fatty liver disease (NAFLD) is a major health issue worldwide, being frequently associated with obesity, unbalanced dietary regimens, and reduced physical activity. Despite their greater adiposity and reduced physical activity, women show a lower risk of developing NAFLD in comparison to men, likely a consequence of a sex-specific regulation of liver metabolism. In the liver, sex differences in the uptake, synthesis, oxidation, deposition, and mobilization of lipids, as well as in the regulation of inflammation, are associated with differences in NAFLD prevalence and progression between men and women. Given the major role of sex hormones in driving hepatic sexual dimorphism, this review will focus on the role of sex hormones and their signaling in the regulation of hepatic metabolism and in the molecular mechanisms triggering NAFLD development and progression.

Keywords: NAFLD; androgen receptor; androgens; estrogen receptors; estrogens; liver; metabolism; sex and gender differences; sex hormones; sexual dimorphism.

Publication types

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

MeSH terms

  • Female
  • Gonadal Steroid Hormones / metabolism*
  • Gonadal Steroid Hormones / physiology
  • Humans
  • Inflammation / metabolism
  • Liver / metabolism*
  • Liver / pathology
  • Male
  • Non-alcoholic Fatty Liver Disease / physiopathology*
  • Obesity / metabolism
  • Sex Characteristics
  • Sex Factors
  • Signal Transduction

Substances

  • Gonadal Steroid Hormones