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DOI | 10.1289/EHP9373 |
Role of Hepatocyte- and Macrophage-Specific in Hepatotoxicity Induced by Diethylhexyl Phthalate in Mice | |
Miao Xu; Yongning Li; Xiaohong Wang; Qiannan Zhang; Lei Wang; Xin Zhang; Wenming Cui; Xiaomin Han; Ning Ma; Haishan Li; Hongyun Fang; Song Tang; Jingguang Li; Zhaoping Liu; Hui Yang; Xudong Jia | |
2022-01-12 | |
发表期刊 | Environmental Health Perspectives |
出版年 | 2022 |
英文摘要 | AbstractBackground:Phthalates may disturb metabolic homeostasis in the liver by interfering with the peroxisome proliferator-activated receptors (PPARs). However, the role of hepatic macrophages in the lipid metabolic dysregulation induced by diethylhexyl phthalate (DEHP) remains unclear. Objectives:We aimed to evaluate the respective role of hepatocyte- and macrophage-specific in the hepatotoxicity induced by DEHP. Methods:Wild-type (WT), hepatocyte-specific knockout (Hep-KO), and macrophage-specific PPAR knockout (Mac-KO) mice were administered DEHP ( body weight) by daily gavage for 28 d, followed by hepatotoxicity examination and macrophage analysis. RNA sequencing and lipid metabolomic analysis were used to characterize the molecular changes in mouse liver. Mouse bone marrow-derived macrophages (BMDMs) and human monocytic THP-1 cell-derived macrophages were used to investigate the mechanistic regulation of macrophages’ polarization by DEHP and mono(2-ethylhexyl) phthalate (MEHP). Results:The levels of hepatic steatosis and triglyceride were significantly higher in the mice treated with DEHP compared with the control mice in the WT and Hep-KO model. Lipid accumulation induced by DEHP was notably attenuated in the Mac-KO mice, but M2-polarization of hepatic macrophages in the Mac-KO mice was significantly higher compared with the WT mice under DEHP treatment. The M2-polarization of BMDMs and human macrophages was suppressed by DEHP and MEHP. Transcriptomic and lipidomic data suggested lower levels of lipid biosynthesis, fatty acid oxidation, and oxidative phosphorylation in the Mac-KO mice compared with the WT and Hep-KO mice under DEHP treatment. Conclusions:Our data suggested that the orchestrated activation of and by MEHP may reprogram hepatic macrophages’ polarization, thereby affecting lipid homeostasis in the mouse liver. Although this conclusion was based on studies conducted in mice and in vitro, these findings may aid in elucidating the health effect of environmental phthalate exposure. https://doi.org/10.1289/EHP9373 |
领域 | 资源环境 |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/345033 |
专题 | 资源环境科学 |
推荐引用方式 GB/T 7714 | Miao Xu,Yongning Li,Xiaohong Wang,et al. Role of Hepatocyte- and Macrophage-Specific in Hepatotoxicity Induced by Diethylhexyl Phthalate in Mice[J]. Environmental Health Perspectives,2022. |
APA | Miao Xu.,Yongning Li.,Xiaohong Wang.,Qiannan Zhang.,Lei Wang.,...&Xudong Jia.(2022).Role of Hepatocyte- and Macrophage-Specific in Hepatotoxicity Induced by Diethylhexyl Phthalate in Mice.Environmental Health Perspectives. |
MLA | Miao Xu,et al."Role of Hepatocyte- and Macrophage-Specific in Hepatotoxicity Induced by Diethylhexyl Phthalate in Mice".Environmental Health Perspectives (2022). |
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