Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver
Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver
复制标题
日本血吸虫感染导致肝脏糖脂代谢重新编程
DOI：
10.1186/s13071-019-3621-6
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发表时间：
2019-08
影响因子：
3.2
通讯作者：
Ji Min Jun
中科院分区：
文献类型：
--
作者：
Xu Zhi Peng;Chang Hao;Ni Yang Yue;Li Chen;Chen Lin;Hou Min;Ji Min Jun
背景：近年来的研究表明，核糖体感染与糖脂代谢异常密切相关。然而，实际的糖脂代谢基因的表达，以及可能的途径，调节糖脂代谢的螺旋体感染liver.Methods：在这项研究中，我们评估了动态表达的糖脂代谢相关的基因和蛋白质在小鼠感染日本血吸虫在指定的时间点，使用实时PCR和免疫荧光。然后，巨噬细胞的培养物用可溶性卵抗原（SEA）处理，以检测与葡萄糖和脂质代谢相关的基因的表达水平，以鉴定响应于这些抗原的巨噬细胞代谢特征。结果：在S. coli培养过程中，肝脏糖酵解相关基因（Ldha、Glut 4、Pkm 2、Glut 1、Pfkfb 3、Aldoc、HK 2、Pfk）表达上调，而糖原合成相关基因（G6pc）表达下调。日本血吸虫感染此外，脂肪酸氧化相关基因（Ucp2、Atp5b、Pparg）的mRNA表达水平显著上调，脂肪酸合成相关基因（Fas、Acc、Scd 1、Srebp1c）和脂质摄取相关基因（Cd 36）的mRNA表达水平显著下调。日本血吸虫感染与这些数据一致，体外SEA刺激显着增强了参与糖酵解和FA氧化的基因表达，但降低了巨噬细胞中与糖异生、FA合成和脂质摄入相关的基因。SEA刺激后巨噬细胞磷酸化AMPK、AKT和mTORC 1水平升高。磷酸化AMPK、AKT和mTORC 1的抑制促进SEA处理的巨噬细胞产生葡萄糖。此外，抑制磷酸化AMPK，而不是磷酸化AKT和磷酸化mTOR，诱导脂质积累在SEA刺激的巨噬细胞。此外，SEA处理的巨噬细胞在体外显著降低肝细胞Acc mRNA的表达。日本血吸虫感染诱导参与肝脏中的catalysis（葡萄糖摄取、糖酵解和脂肪酸氧化）和抑制analysis（糖原合成）的基因的表达水平的动态变化，这可能通过巨噬细胞的代谢状态发生，特别是参与AMPK、AKT和mTORC 1途径的那些。
Background:Recent investigations indicate that schistosome infection is closely associated with aberrant glycolipid metabolism. However, the actual glycolipid metabolism gene expression, as well as the possible pathways that regulate glycolipid metabolism in the schistosome-infected liver, has not been extensively explored.Methods:In this study, we evaluated the dynamic expression of glycolipid metabolism-associated genes and proteins in the livers from mice infected with Schistosoma japonicum at the indicated time points using real-time PCR and immunofluorescence. Then, cultures of macrophages were treated with schistosome soluble egg antigen (SEA) to detect the expression levels of genes associated with glucose and lipid metabolism in order to identify macrophages metabolic characteristics in response to these antigens. Furthermore, SEA-stimulated macrophages were co-cultures with hepatocytes and detected the effects of macrophages on the gene expression of hepatocytes metabolism.Results:The expression of glycolysis-related genes (Ldha, Glut4, Pkm2, Glut1, Pfkfb3, Aldoc, HK2, Pfk) in the liver were upregulated but the gluconeogenesis gene (G6pc) was downregulated during S. japonicum infection. In addition, the mRNA levels of fatty acid (FA) oxidation-related genes (Ucp2, Atp5b, Pparg) in the liver were significantly upregulated; however, the FA synthesis genes (Fas, Acc, Scd1, Srebp1c) and lipid uptake gene (Cd36) were downregulated post-S. japonicum-infection. In consistence with these data, stimulation with SEA in vitro significantly enhanced the gene expression that involved in glycolysis and FA oxidation, but decreased genes related to gluconeogenesis, FA synthesis and lipid uptake in macrophages. The levels of phosphorylated AMPK, AKT and mTORC1 were increased in macrophages after SEA stimulation. Inhibition of phosphorylated AMPK, AKT and mTORC1 promoted SEA-treated macrophages to produce glucose. In addition, suppression of phosphorylated-AMPK, but not phosphorylated-AKT and phosphorylated-mTOR, induced the lipid accumulation in SEA-stimulated macrophages. Furthermore, SEA-treated macrophages significantly reduced the expression of Acc mRNA in hepatocytes in vitro.Conclusions:These findings reveal S. japonicum infection induces dynamic changes in the expression levels of genes involved in catabolism (glucose uptake, glycolysis and fatty acid oxidation) and suppressing anabolism (glycogen synthesis) in the liver, which could occur via macrophages' metabolic states, particularly those involved in the AMPK, AKT and mTORC1 pathways.
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影响因子：
6.7
作者：
Wiria AE;Sartono E;Supali T;Yazdanbakhsh M
通讯作者：
Yazdanbakhsh M
影响因子：
10.9
作者：
Howell, Jessica J.;Manning, Brendan D.
通讯作者：
Manning, Brendan D.
日本血吸虫感染后吡喹酮治疗可维持小鼠肝脏胰岛素敏感性并改善葡萄糖代谢。
影响因子：
3.2
作者：
Luo X;Zhu Y;Liu R;Song J;Zhang F;Zhang W;Xu Z;Hou M;Yang B;Chen L;Ji M
通讯作者：
Ji M
影响因子：
2.1
作者：
H. Giver;S. Vlas;M. V. Johansen;N. Ø. Christensen;Peter Nansen
通讯作者：
H. Giver;S. Vlas;M. V. Johansen;N. Ø. Christensen;Peter Nansen
影响因子：
5.4
作者：
Barron, Luke;Wynn, Thomas A.
通讯作者：
Wynn, Thomas A.