Micheliolide alleviates hepatic steatosis in db/db mice by inhibiting inflammation and promoting autophagy via PPAR-gamma-mediated NF-kappa B and AMPK/mTOR signaling
Micheliolide alleviates hepatic steatosis in db/db mice by inhibiting inflammation and promoting autophagy via PPAR-gamma-mediated NF-kappa B and AMPK/mTOR signaling
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Micheliolide 通过 PPAR-gamma 介导的 NF-kappa B 和 AMPK/mTOR 信号传导抑制炎症并促进自噬，从而减轻 db/db 小鼠的肝脏脂肪变性
DOI：
10.1016/j.intimp.2018.03.036
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发表时间：
2018
影响因子：
5.6
通讯作者：
Long Haibo
中科院分区：
文献类型：
--
作者：
Zhong Juan;Gong Wangqiu;Chen Jing;Qing Yao;Wu Shuyue;Li Hongbei;Huang Chunxi;Chen Yihua;Wang Yuxian;Xu Zhaozhong;Liu Wenting;Li HongYu;Long Haibo
The anti-inflammatory, immunomodulatory, and anticancer effects of micheliolide (MCL) isolated fromMichelia champacawere previously reported, but its role and underlying mechanisms in relieving liver steatosis remain unclear. Herein, we investigated the effects of MCL on hepatic steatosis using a db/db mouse model and lipid mixture (LM)-induced AML12 and LO2 cells. The body and liver weights, food consumption, lipid content and liver aminotransferase levels in serum, the lipid content and inflammatory cytokine levels in liver tissue, and the extent of hepatic steatosis in db/db mice were increased compared with those in db/m mice, and these increases were reversed by MCL treatment. Similarly, MCL also attenuated the inflammatory responses and lipid accumulation in LM-treated AML12 and L02 cells by upregulating PPAR-γ and decreasing p-IкBα and p-NF-κB/p65, thereby inhibiting the NF-κB pathway and reducing lipotoxicity. Furthermore, MCL administration increased LC3B, Atg7 and Beclin-1 expression and the LC3B-II/I ratio in db/db mouse livers and LM-treated AML12 and L02 cells, and these MCL-induced increases were mediated by the activation of PPAR-γ and p-AMPK and inhibition of p-mTOR and induce autophagy. These effects were blocked by PPAR-γ and AMPK inhibitors. Our findings suggest that MCL ameliorates liver steatosis by upregulating PPAR-γ expression, thereby inhibiting NF-κB-mediated inflammation and activating AMPK/mTOR-dependent autophagy.
