Bisphenol S induces brown adipose tissue whitening and aggravates diet-induced obesity in an estrogen-dependent manner
Xue Wen,
Yang Xiao,
Haitao Xiao,
Xueqin Tan,
Beiyi Wu,
Zehua Li,
Ru Wang,
Xuewen Xu,
Tao Li
Affiliations
Xue Wen
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
Yang Xiao
Department of Plastic and Burn Surgery, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China
Haitao Xiao
Department of Plastic and Burn Surgery, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China
Xueqin Tan
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
Beiyi Wu
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
Zehua Li
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
Ru Wang
Department of Plastic and Burn Surgery, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China
Xuewen Xu
Department of Plastic and Burn Surgery, National Clinical Research Center for Geriatrics, West China Hospital of Sichuan University, Chengdu 610041, China; Corresponding author
Tao Li
Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China; Corresponding author
Summary: 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.
