ER dimers bind directly to estrogen response elements of target gene promoters, or indirectly through interaction with other DNA-bound transcription factors. ERs are located as monomers in the cytoplasm in protein complexes involving heat-shock proteins and estrogen binding promotes their dissociation from this complex and ER dimerization.
In classical, genomic, estrogen signaling ERs act as ligand-activated transcription factors, activating or repressing target genes within hours of ligand binding. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.Įstrogen signaling occurs through both genomic and nongenomic mechanisms. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program.
There is extensive evidence supporting the interference of inflammatory activation with metabolism.