Exercise suppresses NLRP3 inflammasome activation in mice with diet-induced NASH: a plausible role of adropin
Exercise suppresses NLRP3 inflammasome activation in mice with diet-induced NASH: a plausible role of adropin
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运动抑制饮食诱导 NASH 小鼠的 NLRP3 炎症小体激活：阿德洛品的合理作用。
DOI：
10.1038/s41374-020-00508-y
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发表时间：
2020-12-02
影响因子：
5
通讯作者：
Li, Liangming
中科院分区：
文献类型：
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作者：
Yang, Wenqi;Liu, Ling;Li, Liangming
这项研究表明，在饮食诱导的非酒精性脂肪性肝炎（NASH）小鼠中，运动可增加促肾上腺素水平并抑制NLRP3炎性体的激活。此外，adropin抑制棕榈酸诱导的肝细胞和库普弗细胞NLRP3炎性体活化。这些结果表明，运动可能通过adropin诱导抑制NLRP3炎性体的激活，从而改善NASH。NLRP3炎性小体激活，可由活性氧（ROS）触发，有助于非酒精性脂肪性肝炎（NASH）的进展。运动是NASH的有效治疗策略。然而，尚未研究运动是否能阻止NASH中NLRP3的激活。在这里，我们研究了运动对高脂肪饮食（HFD）诱导的或蛋氨酸和胆碱缺乏（MCD）饮食诱导的NASH小鼠NLRP3炎性体的影响，并探讨了adropin（一种抑制炎症的代谢肽激素）是否介导了运动诱导的对NLRP3炎性体激活的益处。运动减轻饮食引起的肝脂肪变性、炎症和纤维化。重要的是，运动显著降低了hfd喂养和MCD喂养小鼠NLRP3炎症小体成分的表达，降低了Caspase-1酶活性，使IL-1 β的产生正常化，并抑制了ROS的过量产生。运动引起的NLRP3炎性体抑制伴随着adropin水平的升高。此外，血清adropin水平与血清IL-1 β水平呈负相关。我们进一步探讨了adropin对棕榈酸（PA）处理的肝细胞和库普弗细胞NLRP3炎性体的影响。虽然adropin治疗并没有显著降低所有炎性小体成分的水平，但它降低了PA处理的肝细胞和KCs中活性Caspase-1水平，降低了Caspase-1活性，下调了IL-1 β的表达。此外，pa刺激的肝细胞和Kupffer细胞中的ROS水平在adropin治疗后降低。总之，我们证明了运动对NLRP3炎性小体激活的抑制作用与adropin诱导有关，从而导致NASH的改善。
This study shows that exercise increases adropin levels and inhibits NLRP3 inflammasome activation in mice with diet-induced nonalcoholic steatohepatitis (NASH). Furthermore, adropin suppresses palmitic acid-induced NLRP3 inflammasome activation in hepatocytes and Kupffer cells. These results indicate that exercise may inhibit NLRP3 inflammasome activation via adropin induction, resulting in NASH improvement.NLRP3 inflammasome activation, which can be triggered by reactive oxygen species (ROS), contributes to nonalcoholic steatohepatitis (NASH) progression. Exercise is an effective therapeutic strategy for NASH. However, whether exercise prevents NLRP3 activation in NASH has not been investigated. Here, we investigated the effect of exercise on NLRP3 inflammasome in mice with high-fat diet (HFD)-induced or methionine and choine-deficient (MCD) diet-induced NASH and explored whether adropin, a metabolic peptide hormone shown to inhibit inflammation, mediates an exercise-induced benefit against NLRP3 inflammasome activation. Exercise alleviated diet-induced hepatic steatosis, inflammation, and fibrosis. Importantly, exercise significantly reduced the expression of NLRP3 inflammasome components, decreased Caspase-1 enzymatic activity, normalized IL-1 beta production, and suppressed ROS overproduction in HFD-fed and MCD diet-fed mice. The exercise-elicited NLRP3 inflammasome inhibition was accompanied by increased adropin levels. Moreover, serum adropin levels were negatively correlated with serum IL-1 beta levels. We further explored the effect of adropin on the NLRP3 inflammasome in palmitic acid (PA)-treated hepatocytes and Kupffer cells. Although adropin treatment did not significantly decrease the levels of all inflammasome components, it reduced the active Caspase-1 level, decreased Caspase-1 activity and downregulated IL-1 beta expression in hepatocytes and Kupffer cells (KCs) treated with PA. Moreover, ROS levels in PA-stimulated hepatocytes and Kupffer cells were reduced upon adropin treatment. In summary, we demonstrated that the inhibitory effect of exercise on NLRP3 inflammasome activation was associated with adropin induction, resulting in NASH improvement.