TCEP
脂肪变性
脂肪生成
化学
内科学
下调和上调
内分泌学
生物化学
脂质代谢
医学
基因
催化作用
磷化氢
作者
Daqian Yang,Xiangjuan Wei,Ziyi Zhang,Xi Chen,Ruijiao Zhu,Yuri Oh,Ning Gu
标识
DOI:10.1016/j.cbi.2022.110027
摘要
Tris (2-chloroethyl) phosphate (TCEP) is the most commonly detective organophosphate flame retardant in surroundings. TCEP is also evidenced as endocrine disrupting chemicals and has potential adverse effects on metabolic diseases. In this study, we hypothesized that metabolic diseases are adverse outcomes of TCEP exposure. Adult ICR mice was daily treated with TCEP (20 mg/kg and 60 mg/kg, higher than expected level in people) by gavage administration for 9 weeks. The results demonstrate that TCEP promoted body weight gain, hypertriglyceridemia, and hepatic steatosis, consistent with upregulation of hepatic lipogenesis-related gene expression. Moreover, TCEP altered the levels of several hepatic metabolites, especially bile acids and downregulated bile acid synthesis pathways. Intriguingly, we found a marked downregulation of the bile acid nuclear reporter, FXR, in TCEP-exposed livers. Mechanistically, TCEP directly interacted with FXR at Lys335 and Lys336. Further studies in this work elucidate the mechanisms of long-term TCEP exposure on hepatic steatosis and obesity in mice via FXR-mediated lipid accumulation. Our results provide insight into the possibility of intermediate TCEP exposure in causing metabolic diseases.
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