Zeng Tianshu, Zhou Jing, He Linzheng, Zheng Juan, Chen Lulu, Wu Chaodong, Xia Wenfang
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Endocrinology, Chengdu First People's Hospital, Chengdu, 610000, China.
PLoS One. 2016 Mar 1;11(3):e0149677. doi: 10.1371/journal.pone.0149677. eCollection 2016.
Inflammation critically contributes to the development of various metabolic diseases. However, the effects of inhibiting inflammatory signaling on hepatic steatosis and insulin resistance, as well as the underlying mechanisms remain obscure. In the current study, male C57BL/6J mice were fed a chow diet or high-fat diet (HFD) for 8 weeks. HFD-fed mice were respectively treated with p65 siRNA, non-silence control siRNA or vehicle every 4th day for the last 4 weeks. Vehicle-treated (HF) and non-silence siRNA-treated (HFNS) mice displayed overt inflammation, hepatic steatosis and insulin resistance compared with chow-diet-fed (NC) mice. Upon treatment with NF-κB p65 siRNA, HFD-fed (HFPS) mice were protected from hepatic steatosis and insulin resistance. Furthermore, Atg7 and Beclin1 expressions and p-AMPK were increased while p-mTOR was decreased in livers of HFPS mice in relative to HF and HFNS mice. These results suggest a crosslink between NF-κB signaling pathway and liver AMPK/mTOR/autophagy axis in the context of hepatic steatosis and insulin resistance.
炎症在多种代谢性疾病的发展过程中起着关键作用。然而，抑制炎症信号传导对肝脂肪变性和胰岛素抵抗的影响及其潜在机制仍不清楚。在本研究中，雄性C57BL/6J小鼠分别给予普通饮食或高脂饮食（HFD）8周。在最后4周，每隔4天给高脂饮食喂养的小鼠分别注射p65 siRNA、非沉默对照siRNA或溶剂。与普通饮食喂养的（NC）小鼠相比，溶剂处理的（HF）和非沉默siRNA处理的（HFNS）小鼠表现出明显的炎症、肝脂肪变性和胰岛素抵抗。在用NF-κB p65 siRNA处理后，高脂饮食喂养的（HFPS）小鼠免受肝脂肪变性和胰岛素抵抗的影响。此外，相对于HF和HFNS小鼠，HFPS小鼠肝脏中Atg7和Beclin1的表达以及p-AMPK增加，而p-mTOR减少。这些结果表明，在肝脂肪变性和胰岛素抵抗的背景下，NF-κB信号通路与肝脏AMPK/mTOR/自噬轴之间存在交联。
