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Effects of peptidoglycan on the development of steatohepatitis.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ( IF 4.8 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.bbalip.2019.158595
Meiling Jin 1 , Yihong Lai 1 , Peili Zhao 1 , Qian Shen 1 , Wen Su 1 , Yue Yin 2 , Weizhen Zhang 3
Affiliation  

Elevating evidences suggested roles of peptidoglycan (PGN) for the insulin resistance, metabolic inflammation and liver disorders. But, whether PGN affects the occurrence of steatohepatitis remains unclear. Here, we reported that subcutaneous infusion of purified PGN for 4 weeks significantly increased hepatic levels of triglyceride, inflammation and fibrosis in mice fed normal chow. These alterations were associated with raise in circulating triglyceride, cholesterol, insulin content and inflammatory cytokines. PGN significantly increased triglyceride contents as well as lipogenesis related genes in primary hepatocytes or LO2 cells, either in basal or oleic acid treated conditions. Administration of PGN stimulated the expression of NOD2, as well as phosphorylation of p65 and IκBα, leading to subsequent nuclear translocation of p65. Over-expression of NOD2 significantly enhanced the phosphorylation of p65, levels of nuclear PPARγ and SREBP1, followed by increase in triglyceride contents in LO2 cells treated with or without oleic acid. Further, over-expression of NOD2 significantly augmented the up-regulation of PPARγ induced by rosiglitazone. Inhibition of NFκB blocked the effect of NOD2 on the upregulation of PPARγ. Our study demonstrates that PGN stimulates hepatic lipogenesis by NOD2-NFκB-PPARγ signaling. PGN from intestinal microbiota is thus sufficient to induce the progression of steatohepatitis.

中文翻译:

肽聚糖对脂肪性肝炎发展的影响。

越来越多的证据表明肽聚糖(PGN)在胰岛素抵抗,代谢性炎症和肝脏疾病中的作用。但是,PGN是否影响脂肪性肝炎的发生尚不清楚。在这里,我们报道皮下注射纯化的PGN 4周可显着增加正常食物喂养小鼠的肝中甘油三酸酯水平,炎症和纤维化。这些变化与循环甘油三酸酯,胆固醇,胰岛素含量和炎性细胞因子的升高有关。在基础或油酸治疗的条件下,PGN显着增加了原代肝细胞或LO2细胞中甘油三酸酯的含量以及与脂肪生成相关的基因。施用PGN刺激了NOD2的表达,以及p65和IκBα的磷酸化,导致p65随后发生核转位。NOD2的过表达显着增强了p65的磷酸化,核PPARγ和SREBP1的水平,随后增加了用或不用油酸处理的LO2细胞中甘油三酸酯的含量。此外,NOD2的过表达显着增强了罗格列酮诱导的PPARγ的上调。抑制NFκB阻断了NOD2对PPARγ上调的作用。我们的研究表明,PGN通过NOD2-NFκB-PPARγ信号传导刺激肝脏脂肪生成。因此,来自肠道菌群的PGN足以诱导脂肪性肝炎的进展。NOD2的过表达显着增强了罗格列酮诱导的PPARγ的上调。抑制NFκB阻断了NOD2对PPARγ上调的作用。我们的研究表明,PGN通过NOD2-NFκB-PPARγ信号传导刺激肝脏脂肪生成。因此,来自肠道菌群的PGN足以诱导脂肪性肝炎的进展。NOD2的过表达显着增强了罗格列酮诱导的PPARγ的上调。抑制NFκB阻断了NOD2对PPARγ上调的作用。我们的研究表明,PGN通过NOD2-NFκB-PPARγ信号传导刺激肝脏脂肪生成。因此,来自肠道菌群的PGN足以诱导脂肪性肝炎的进展。
更新日期:2020-01-14
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