ERα in the Control of Mitochondrial Function and Metabolic Health

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, ER alpha) 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 ER alpha on mitochondrial form and function and present how these actions of the receptor govern metabolic homeostasis. Studies identifying ER alpha-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.