2. Academic Validation
  3. Bisphenol S induces brown adipose tissue whitening and aggravates diet-induced obesity in an estrogen-dependent manner

Bisphenol S induces brown adipose tissue whitening and aggravates diet-induced obesity in an estrogen-dependent manner

  • Cell Rep. 2023 Dec 1;42(12):113504. doi: 10.1016/j.celrep.2023.113504.
Xue Wen 1,  Yang Xiao 2,  Haitao Xiao 2,  Xueqin Tan 1,  Beiyi Wu 1,  Zehua Li 1,  Ru Wang 2,  Xuewen Xu 3,  Tao Li 4
Affiliations

Affiliations

  • 1 Department of Plastic and Burn Surgery, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China; Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China.
  • 2 Department of Plastic and Burn Surgery, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China.
  • 3 Department of Plastic and Burn Surgery, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China. Electronic address: xxw_0826@163.com.
  • 4 Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China. Electronic address: scutaoli1981@scu.edu.cn.
PMID: 38041811 DOI: 10.1016/j.celrep.2023.113504
Abstract

Bisphenol S (BPS) exposure has been implied epidemiologically to increase obesity risk, but the underlying mechanism is unclear. Here, we propose that BPS exposure at an environmentally relevant dose aggravates diet-induced obesity in female mice by inducing brown adipose tissue (BAT) whitening. We explored the underlying mechanism by which KDM5A-associated demethylation of the trimethylation of lysine 4 on histone H3 (H3K4me3) in thermogenic genes is overactivated in BAT upon BPS exposure, leading to the reduced expression of thermogenic genes. Further studies have suggested that BPS activates KDM5A transcription in BAT by binding to Glucocorticoid Receptor (GR) in an estrogen-dependent manner. Estrogen-estrogen receptors facilitate the accessibility of the KDM5A gene promoter to BPS-activated GR by recruiting the activator protein 1 (AP-1) complex. These results indicate that BAT is another important target of BPS and that targeting KDM5A-related signals may serve as an approach to counteract the BPS-induced susceptivity to obesity.

Keywords

CP: Metabolism; CP: Molecular biology; bisphenol S; brown adipose tissue; lysine demethylase 5A; obesity; trimethylation of lysine 4 on histone H3.

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