The impact of ERα action on muscle metabolism and insulin sensitivity – Strong enough for a man, made for a woman

Abstract

BackgroundThe incidence of chronic disease is elevated in women after menopause. Natural variation in muscle expression of the estrogen receptor (ER)α is inversely associated with plasma insulin and adiposity. Moreover, reduced muscle ERα expression levels are observed in women and animals presenting clinical features of the metabolic syndrome (MetSyn). Considering that metabolic dysfunction impacts nearly a quarter of the U.S. adult population and elevates chronic disease risk including type 2 diabetes, heart disease, and certain cancers, treatment strategies to combat metabolic dysfunction and associated pathologies are desperately needed.Scope of the reviewThis review will provide evidence supporting a critical and protective role for skeletal muscle ERα in the regulation of metabolic homeostasis and insulin sensitivity, and propose novel ERα targets involved in the maintenance of metabolic health.Major conclusionsStudies identifying ERα-regulated pathways essential for disease prevention will lay the important foundation for the rational design of novel therapeutics to improve the metabolic health of women while limiting secondary complications that have plagued traditional hormone replacement interventions.

Adaptive Fat Oxidation Is Coupled with Increased Lipid Storage in Adipose Tissue of Female Mice Fed High Dietary Fat and Sucrose

“…The role of estrogen was not tested in our study, but there is abundant evidence that estrogens stimulate a range of transcriptional and post-translational changes that stimulate fatty acid utilization in the liver and skeletal muscle [48][49][50][51] and promote lipid storage in subcutaneous but not visceral fat in women [52]. The impact of estrogen on metabolism in females likely contributes to the relative protection from ectopic lipid accumulation found in MetS, but the adaptations to the HFS diet observed in our study occurred over a relatively short exposure when considered as a model of the chronic dietary intake of the Western diet in women.…”

Gene X environment: the cellular environment governs the transcriptional response to environmental chemicals

“…The sexual dimorphic response specific to ER action has been associated with the development of or protection from certain diseases (e.g., metabolic syndrome and autoimmune diseases) [33][34][35][36]. As such, animal studies have demonstrated that exogenous exposures that inappropriately alter ER signaling can increase the relative risk for these diseases [37][38][39].…”

Schützen Östrogene Frauen vor der Fettleber?

“…Die Östrogenrezeptordichte (Östrogenrezeptor-Alpha) der Skelettmuskulatur ist positiv assoziiert mit der Insulinsensitivität des Skelettmuskels. Bei Frauen mit metabolischem Syndrom sowie postmenopausalen Frauen ist die Östrogenrezeptorexpression der Skelettmuskulatur reduziert und nimmt im Verlauf der Postmenopause weiter ab [11,12]. Somit kommt es in der Folge zu einer Abnahme der Insulinsensitivität mit vermehrtem Rückfluss von Substraten und gesteigerter Substratverfügbarkeit an der Leber, was wiederum die DNL begünstigt.…”