4.6 Article

Steatosis and Metabolic Disorders Associated with Synergistic Activation of the CAR/RXR Heterodimer by Pesticides

期刊

CELLS
卷 12, 期 8, 页码 -

出版社

MDPI
DOI: 10.3390/cells12081201

关键词

CAR; RXR; nuclear; receptor; pesticides; steatosis; NAFLD; tributyltin; metabolism; synergism

向作者/读者索取更多资源

The nuclear receptor CAR, in partnership with RXR, regulates hepatic genes involved in detoxication and energy metabolism. Activation of CAR can lead to metabolic disorders, including non-alcoholic fatty liver disease, by promoting liver lipogenesis. In this study, synergistic activations of CAR/RXR heterodimer were observed in mice when exposed to certain pesticides, resulting in steatosis and metabolic disruption characterized by increased cholesterol and decreased free fatty acid levels.
The nuclear receptor, constitutive androstane receptor (CAR), which forms a heterodimer with the retinoid X receptor (RXR), was initially reported as a transcription factor that regulates hepatic genes involved in detoxication and energy metabolism. Different studies have shown that CAR activation results in metabolic disorders, including non-alcoholic fatty liver disease, by activating lipogenesis in the liver. Our objective was to determine whether synergistic activations of the CAR/RXR heterodimer could occur in vivo as described in vitro by other authors, and to assess the metabolic consequences. For this purpose, six pesticides, ligands of CAR, were selected, and Tri-butyl-tin (TBT) was used as an RXR agonist. In mice, CAR's synergic activation was induced by dieldrin associated with TBT, and combined effects were induced by propiconazole, bifenox, boscalid, and bupirimate. Moreover, a steatosis, characterized by increased triglycerides, was observed when TBT was combined with dieldrin, propiconazole, bifenox, boscalid, and bupirimate. Metabolic disruption appeared in the form of increased cholesterol and lowered free fatty acid plasma levels. An in-depth analysis revealed increased expression of genes involved in lipid synthesis and lipid import. These results contribute to the growing understanding of how environmental contaminants can influence nuclear receptor activity and associated health risks.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据