4.7 Article

Farnesoid X receptor overexpression prevents hepatic steatosis through inhibiting AIM2 inflammasome activation in nonalcoholic fatty liver disease

出版社

ELSEVIER
DOI: 10.1016/j.bbadis.2023.166930

关键词

Farnesoid X receptor (FXR; AIM2 inflammasome; High -fat diet; Nonalcoholic fatty liver disease; Oxidative stress

向作者/读者索取更多资源

This study found that FXR is significantly reduced in the livers of NAFLD patients. Overexpression of FXR can improve NAFLD and inhibit oxidative stress and AIM2 inflammasome activation.
Oxidative stress-mediated activation of inflammasome has a significant effect on the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Farnesoid X receptor (NR1H4, FXR) has been implicated in biological function and many diseases, including NAFLD. The regulatory effect of FXR on oxidative stress and whether this process is related with the activation of absent melanoma 2 (AIM2) inflammasome in NAFLD remain unclear. In the present research, we confirmed that FXR in the livers of steatosis patients is significantly reduced compared with normal liver tissue by using the Gene Expression Omnibus (GEO) database and a palmitic acid (PA) - mediated steatosis model in AML-12 cells. Under the premise of ensuring the same food intake as the control group, overexpression of FXR in mice attenuated HFD-mediated weight gain and liver steatosis, facilitated lipid metabolism, improved fatty acid 0-oxidation, lipolysis, and reduced fatty acid synthesis and intake, which also inhibited the activation of AIM2 inflammasome. Overexpression of FXR alleviated PA-induced triglyceride (TG) accumulation, imbalance of lipid homeostasis, and the activation of AIM2 inflammasome in hepatic steatosis cells, while FXR knockdown appeared the opposite effects. FXR overexpression suppressed PA- and HFD-induced oxidative stress, but FXR siRNA demonstrated the opposite influence. The decreased ROS generation may be the reason why FXR weakens AIM2 activation when a fatty acid overload occurs. In conclusion, our results confirm that other than regulating lipid homeostasis and blocking NLRP3 inflammasome activation, FXR improves hepatic steatosis by a novel mechanism that inhibits oxidative stress and AIM2 inflammasome activation.

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

4.7
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