Estrogen Signaling in Metabolic Inflammation

Figure 3

Different models have shown the influence of estrogens on metabolic-related inflammation. Loss of/decreased estrogen signaling through decreased production of estrogens or ERalpha, ERalpha/beta, or GPER inactivation promotes metabolic dysfunction revealed by visceral obesity, insulin resistance, dyslipidemia, inflammatory activation, and nonalcoholic fatty liver disease. On the other hand, promoting maintenance of estrogen signaling through hormone replacement therapy, blocking estrogen inactivation by estrogen sulfotransferase or increasing its reactivation from the estrogen-sulfate circulating pool by steroid sulfatase induction, tends to counteract metabolic dysfunction. Interestingly, inactivation of ERbeta also promotes metabolic health, showing the opposite metabolic effects mediated by both ER receptors. ER: estrogen receptor; GPER: G protein-coupled estrogen receptor; HRT: hormone replacement therapy; NAFLD: nonalcoholic fatty liver disease.