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  3. Estrogen receptor α mediated M1/M2 macrophages polarization plays a critical role in NASH of female mice

Estrogen receptor α mediated M1/M2 macrophages polarization plays a critical role in NASH of female mice

  • Biochem Biophys Res Commun. 2022 Mar 12;596:63-70. doi: 10.1016/j.bbrc.2022.01.085.
Zhiping Shu 1,  Guopeng Zhang 1,  Xiaohua Zhu 2,  Wenqian Xiong 3
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China.
  • 2 Department of Nuclear Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 JieFang Avenue, Wuhan, 430022, China. Electronic address: [email protected].
  • 3 Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 JieFang Avenue, Wuhan, 430030, China. Electronic address: [email protected].
PMID: 35114586 DOI: 10.1016/j.bbrc.2022.01.085
Abstract

Owing to lacking protective effect of estrogen, OVX mice have higher risk of non-alcoholic fatty liver disease compared with normal female mice, when fed with high fat diet. Our study was to explore how estrogen protect against nonalcoholic steatohepatitis in female mice. We found that, lacking estrogen, M1 macrphages was activated and promoted steatohepatitis in obese OVX mice. And, ERα was responsible for estrogen to inhibit M1 macrphages activation and steatohepatitis. ERα knockdown aggravated M1 macrophages infiltration by transcriptionally upregulated its CCR2 expression. CCR2 Antagonist effectively improved nonalcoholic steatohepatitis, ER stress and Insulin resistance in ERα knockdown obese female mice. These results demonstrated ERα mediated M1 macrophages activation played a key role in nonalcoholic steatohepatitis.

Keywords

CCR2; ERα; M1 macrophages; Nonalcoholic steatohepatitis; Transcriptional regulation.

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