This study examines the effects of chicoric acid (CA) on nonalcoholic fatty liver disease (NAFLD) in high-fat-diet- (HFD-) fed C57BL/6 mice. CA treatment decreased body weight and white adipose weight, mitigated hyperglycemia and dyslipidemia, and reduced hepatic steatosis in HFD-fed mice. Moreover, CA treatment reversed HFD-induced oxidative stress and inflammation both systemically and locally in the liver, evidenced by the decreased serum malondialdehyde (MDA) abundance, increased serum superoxide dismutase (SOD) activity, lowered in situ reactive oxygen species (ROS) in the liver, decreased serum and hepatic inflammatory cytokine levels, and reduced hepatic inflammatory cell infiltration in HFD-fed mice. In addition, CA significantly reduced lipid accumulation and oxidative stress in palmitic acid- (PA-) treated HepG2 cells. In particular, we identified AMPK as an activator of Nrf2 and an inactivator of NFκB. CA upregulated AMPK phosphorylation, the nuclear protein level of Nrf2, and downregulated NFκB protein level both in HFD mice and PA-treated HepG2 cells. Notably, AMPK inhibitor compound C blocked the regulation of Nrf2 and NFκB, as well as ROS overproduction mediated by CA in PA-treated HepG2 cells, while AMPK activator AICAR mimicked the effects of CA. Similarly, Nrf2 inhibitor ML385 partly blocked the regulation of antioxidative genes and ROS overproduction by CA in PA-treated HepG2 cells. Interestingly, high-throughput pyrosequencing of 16S rRNA suggested that CA could increase Firmicutes-to-Bacteroidetes ratio and modify gut microbial composition towards a healthier microbial profile. In summary, CA plays a preventative role in the amelioration of oxidative stress and inflammation via the AMPK/Nrf2/NFκB signaling pathway and shapes gut microbiota in HFD-induced NAFLD.

中文翻译：

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甲壳酸通过AMPK / Nrf2 /NFκB信号通路改善非酒精性脂肪性肝病，并恢复高脂饮食喂养小鼠的肠道菌群。

这项研究检查了高糖饮食（HFD-）喂养的C57BL / 6小鼠中甲壳酸（CA）对非酒精性脂肪肝疾病（NAFLD）的影响。CA治疗可降低喂食HFD的小鼠的体重和白脂肪的重量，减轻高血糖症和血脂异常，并减少肝脂肪变性。此外，CA治疗可逆转HFD诱导的肝脏全身和局部氧化应激和炎症，这可通过降低血清丙二醛（MDA）丰度，增加血清超氧化物歧化酶（SOD）活性，降低原位来证明喂食HFD的小鼠肝脏中的活性氧（ROS），降低血清和肝炎性细胞因子水平以及减少肝炎性细胞浸润。此外，CA显着降低了棕榈酸-（PA-）处理的HepG2细胞的脂质蓄积和氧化应激。特别地，我们鉴定作为AMPK的Nrf2的活化剂和NF的灭活κ B. CA上调AMPK磷酸化，Nrf2的核蛋白质水平，下调NF κ无论在HFD小鼠和PA处理的HepG2细胞B蛋白水平。值得注意的是，AMPK抑制剂化合物C阻断的Nrf2和NF的调节κB，以及PA介导的HepG2细胞中CA介导的ROS过度生产，而AMPK激活物AICAR模仿了CA的作用。同样，Nrf2抑制剂ML385在PA处理的HepG2细胞中部分阻断了CA对抗氧化基因的调节和ROS的过量生产。有趣的是，高通量的16S rRNA焦磷酸测序表明，CA可以提高菌毛比拟杆菌的比例，并使肠道微生物的组成朝着更健康的微生物方向发展。总之，CA起着氧化应激和炎症的改善通过AMPK / Nrf2的/ NF一种预防性的作用κ乙信号通路和形状在HFD诱导的NAFLD肠道菌群。