Design and synthesis of ERα agonists: Effectively reduce lipid accumulation

Jinfei Yang; Weiwei Yao; Huihui Yang; Yajing Shen; Yuanyuan Zhang

doi:10.3389/fchem.2022.1104249

Design and synthesis of ERα agonists: Effectively reduce lipid accumulation

Front Chem. 2022 Dec 8:10:1104249. doi: 10.3389/fchem.2022.1104249. eCollection 2022.

Authors

Jinfei Yang¹, Weiwei Yao¹, Huihui Yang¹, Yajing Shen¹, Yuanyuan Zhang²

Affiliations

¹ School of Health and Life Sciences, University of Health and Rehabilitation Sciences, Qingdao, China.
² West China School of Pharmacy, Sichuan University, Chengdu, China.

Abstract

In recent years, the incidence of non-alcoholic fatty liver disease (NAFLD) has been increasing worldwide. Hepatic lipid deposition is a major feature of NAFLD, and insulin resistance is one of the most important causes of lipid deposition. Insulin resistance results in the disruption of lipid metabolism homeostasis characterized by increased lipogenesis and decreased lipolysis. Estrogen receptor α (ERα) has been widely reported to be closely related to lipid metabolism. Activating ERa may be a promising strategy to improve lipid metabolism. Here, we used computer-aided drug design technology to discover a highly active compound, YRL-03, which can effectively reduce lipid accumulation. Cellular experimental results showed that YRL-03 could effectively reduce lipid accumulation by targeting ERα, thereby achieving alleviation of insulin resistance. We believe this study provides meaningful guidance for future molecular development of drugs to prevent and treat NAFLD.

Keywords: ERα; NAFLD; agonists; lipid accumulation; liver disease.