Reduced hepatic AdipoR2 by increased glucocorticoid mediates effect of psychosocial stress to elevate serum cholesterol

作者全名：Guo, Qi Wei; Lin, Jia; Shen, Yi Lin; Zheng, Yan Jiang; Chen, Xu; Su, Mi; Zhang, Ji Cheng; Wang, Jin Hua; Tang, Hui; Su, Guo Ming; Li, Zheng Ke; Fang, Ding Zhi

作者地址：[Guo, Qi Wei; Lin, Jia; Shen, Yi Lin; Zheng, Yan Jiang; Chen, Xu; Su, Mi; Zhang, Ji Cheng; Wang, Jin Hua; Su, Guo Ming; Fang, Ding Zhi] Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Dept Biochem & Mol Biol, Chengdu 610041, Peoples R China; [Tang, Hui] Chongqing Med Univ, Affiliated Hosp 2, Inst Viral Hepatitis, Chongqing, Peoples R China; [Li, Zheng Ke] Univ Texas MD Anderson Canc Ctr, Dept Thorac & Head & Neck Med Oncol, Houston, TX USA

通信作者：Fang, DZ (通讯作者)，Sichuan Univ, West China Sch Basic Med Sci & Forens Med, Dept Biochem & Mol Biol, Chengdu 610041, Peoples R China.

来源：MOLECULAR AND CELLULAR ENDOCRINOLOGY

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:001250654200001

JCR分区：Q2

影响因子：3.8

年份：2024

卷号：592

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Psychosocial stress; Glucocorticoid; Liver; Adiponectin receptor 2; Serum cholesterol

摘要：Understanding the effects of psychosocial stress on serum cholesterol may offer valuable insights into the relationship between psychological disorders and endocrine diseases. However, these effects and their underlying mechanisms have not been elucidated yet. Here we show that serum corticosterone, total cholesterol and lowdensity lipoprotein cholesterol (LDL-C) are elevated in a mouse model of psychosocial stress. Furthermore, alterations occur in AdipoR2-mediated AMPK and PPAR alpha signaling pathways in liver, accompanied by a decrease in LDL-C clearance and an increase in cholesterol synthesis. These changes are further verified in wild -type and AdipoR2 overexpression HepG2 cells incubated with cortisol and AdipoR agonist, and are finally confirmed by treating wild -type and hepatic -specific AdipoR2 overexpression mice with corticosterone. We conclude that increased glucocorticoid mediates the effects of psychosocial stress to elevate serum cholesterol by inhibiting AdipoR2-mediated AMPK and PPAR alpha signaling to decrease LDL-C clearance and increase cholesterol synthesis in liver.

基金机构：National Natural Science Founda- tion of China [81974043]; Major Project of Sichuan for Science and Technology [2022YFH0025]

基金资助正文：This study was supported by the National Natural Science Founda- tion of China (grant no. 81974043) and Major Project of Sichuan for Science and Technology (grant no. 2022YFH0025) . Professor Ding Zhi Fang is the recipient of the grant.