Danthron ameliorates obesity and MAFLD through activating the interplay between PPAR?/RXR? heterodimer and adiponectin receptor 2

文献类型： 外文期刊

第一作者： Ma, Chuanrui

作者： Ma, Chuanrui;Zhang, Chao;Zhang, Jing;Zhao, Linna;Wu, Han;Kang, Lin;Yang, Shu;Yang, Shu;Ma, Chuanrui;Zhang, Chao;Zhang, Jing;Zhao, Linna;Ma, Chuanrui;Xia, Ronglin;Zhang, Jing;Zhao, Linna;Wu, Han;Xia, Ronglin;Wang, Zhongyan;Wei, Lingling

作者机构：

关键词： Danthron; Obesity; Hepatic steatosis; AdipoR2; AMPK?; PPAR?

期刊名称：BIOMEDICINE & PHARMACOTHERAPY （ 影响因子：4.545； 五年影响因子：4.392 ）

ISSN： 0753-3322

年卷期： 2021 年 137 卷

页码：

收录情况： SCI

摘要： Obesity and associated metabolic associated fatty liver diseases (MAFLD) are strongly associated with dysfunction of glucose and lipid metabolism. AMPK? and PPAR? are key regulators in the lipid and glucose homeostasis, indicating that novel agents to activate them are promising therapeutic approaches for metabolic syndrome. Noticeably, as a natural anthraquinone derivative extracted from rhubarb , danthron can activate AMPK? in vitro. However, the protective effect of danthron on obesity and associated MAFLD in vivo, as well as the underlying mechanism remains unknown. In this study, obesity and associated MAFLD was induced in C57BL/6J mice by high fat diet (HFD), which were subjected to evaluations on the parameters of systematic metabolism. Simultaneously, the molecular mechanism of danthron on lipid metabolism was investigated in 3T3 L1-derived adipocytes and HepG2 cells in vitro. In vivo , danthron significantly attenuated the obesity and MAFLD by enhancing hepatic fatty acid oxidation, decreasing lipid synthesis, and promoting mitochondrial homeostasis. Mechanistically, danthron significantly promoted combination of RXR? and PPAR?, enhanced the binding of RXR?/PPAR? heterodimer to the promoter of adiponectin receptor 2 (AdipoR2), by which activating the AMPK? and PPAR? pathway. Moreover, PPAR? and AdipoR2 can interplay in a loop style. Collectively, this study demonstrates that danthron can substantially ameliorate obesity and associated hepatic steatosis via AdipoR2mediated dual PPAR?/AMPK? activation, which suggests that danthron might be a novel therapeutic approach for inhibition of obesity and hepatic steatosis.

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