AUTHOR=Zhu Bao-Ting , Liao Qing-Qing , Tian Hai-Ying , Yu Dao-Jiang , Xie Teng , Sun Xi-Lu , Zhou Xin-Meng , Han Ying-Xuan , Zhao Yu-Jie , El-Kassas Mohamed , Liu Xiu-Xiu , Sun Xiao-Dong , Zhang Yuan-Yuan TITLE=Estrogen: the forgotten player in metaflammation JOURNAL=Frontiers in Pharmacology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1478819 DOI=10.3389/fphar.2024.1478819 ISSN=1663-9812 ABSTRACT=

Metaflammation is low-grade inflammation triggered by chronic metabolic imbalance and caused by dysregulated metabolites in metabolic inflammatory syndrome (MIS), which includes four diseases: obesity, type 2 diabetes mellitus (T2DM), atherosclerosis (AS), and nonalcoholic fatty liver diseases (NAFLD, recently proposed to be replaced by metabolic dysfunction-associated steatotic liver disease, MASLD). These diseases exhibit apparent sex dimorphism as regards MIS. Estrogen not only plays a crucial role in gender differences in adults but also possesses an anti-inflammatory effect on many metabolic diseases. In this study, we present a prediction of the differential proteins and signal transduction of estrogen in MIS through network pharmacology and review the validated studies on obesity, T2DM, AS, and NAFLD. Subsequently, we compared them to obtain valuable targets, identify current gaps, and provide perspectives for future research on the mechanisms of estrogen in metaflammation.