背景:由于脂肪组织中的慢性炎症引起的代谢性疾病的发病率上升归因于诸如高脂饮食(HFD)等因素。先前的研究表明,竹节参总皂苷(TSPJ)可以减轻HFD诱导的脂肪细胞炎症,但潜在的机制仍不清楚。在这项工作中,我们探讨了TSPJ降低脂肪细胞炎症反应的分子机制.
方法:我们首先建立了C57BL/6小鼠和3T3-L1脂肪细胞模型。将与质粒包装的慢病毒通过尾静脉或脂肪细胞注射到小鼠中,以产生具有miR155敲低和过表达的体内和体外模型。给小鼠喂食HFD以引发炎症,并通过管饲法给予TSPJ(25mg/kg·d和75mg/kg·d)。脂肪细胞用棕榈酸(PA)处理以引发炎症反应,然后用TSPJ(25μg/ml和50μg/ml)处理。最后,miR155的表达,炎症因子,研究了SOCS1和NFκB通路相关蛋白。
结果:TSPJ在体内和体外均显着抑制炎症相关基因的表达和脂肪细胞中miR155的表达。双荧光素酶报告基因分析显示miR155介导了SOCS1的下调。TSPJ显著抑制和上调NFκB蛋白和SOCS1蛋白的磷酸化,分别。
结论:TSPJ抑制miR155上调SOCS1表达,随后抑制NFκB信号通路,从而减轻HFD小鼠脂肪细胞的炎症反应。
BACKGROUND: The rising incidence of metabolic diseases due to chronic inflammation in the adipose tissue has been attributed to factors such as high fat diet (HFD). Previous studies have demonstrated that the total saponins from Panax japonicus (TSPJ) can reduce HFD-induced adipocyte inflammation, but the underlying mechanism remains unclear. In this work, we explored the molecular mechanism by which TSPJ reduces inflammation response in adipocytes.
METHODS: We first established C57BL/6 mouse and 3T3-L1 adipocyte models. Lentiviruses packaged with the plasmids were injected into mice through the tail vein or into adipocytes to generate the in vivo and in vitro models with miR155 knockdown and overexpression. The mice were fed with HFD to trigger inflammation and administered TSPJ (25 mg/kg∙d and 75 mg/kg∙d) by gavage. The adipocytes were treated with palmitic acid (PA) to trigger inflammation response, then treated with TSPJ (25 μg/ml and 50 μg/ml). Finally, the expression of miR155, inflammatory factors, SOCS1, and NFκB pathway-related proteins was explored.
RESULTS: TSPJ significantly inhibited the expression of inflammation-related genes and the miR155 expression in adipocytes both in vitro and in vivo. The dual luciferase reporter gene assay revealed that miR155 mediated the downregulation of SOCS1. TSPJ significantly inhibited and upregulated the phosphorylation of the NFκB protein and the SOCS1 proteins, respectively.
CONCLUSIONS: TSPJ inhibits miR155 to upregulate the SOCS1 expression, which subsequently inhibits the NFκB signaling pathway, thereby mitigating the inflammatory response in the adipocytes of HFD mice.