ERα in the Control of Mitochondrial Function and Metabolic Health

Trends Mol Med. 2021 Jan;27(1):31-46. doi: 10.1016/j.molmed.2020.09.006. Epub 2020 Oct 2.

Abstract

Decrements in metabolic health elevate disease risk, including type 2 diabetes, heart disease, and certain cancers. Thus, treatment strategies to combat metabolic dysfunction are needed. Reduced ESR1 (estrogen receptor, ERα) expression is observed in muscle from women, men, and animals presenting clinical features of the metabolic syndrome. Human studies of natural expression of ESR1 in metabolic tissues show that muscle expression of ESR1 is positively correlated with markers of metabolic health, including insulin sensitivity. Herein, we highlight the important impact of ERα on mitochondrial form and function and present how these actions of the receptor govern metabolic homeostasis. Studies identifying ERα-regulated pathways for disease prevention will lay the foundation for the design of novel therapeutics to improve the health of women while limiting secondary complications that have plagued traditional hormone replacement interventions.

Keywords: ERalpha; estrogen action; metabolic health; mitochondrial function; muscle insulin sensitivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Disease Susceptibility
  • Energy Metabolism*
  • Estrogen Receptor alpha / genetics
  • Estrogen Receptor alpha / metabolism*
  • Homeostasis*
  • Humans
  • Insulin Resistance
  • Metabolic Diseases / etiology*
  • Metabolic Diseases / metabolism*
  • Mitochondria / genetics
  • Mitochondria / metabolism*
  • Organ Specificity

Substances

  • Estrogen Receptor alpha