Microarray analysis of lncRNA and mRNA reveals lipogenesis inhibition along with metabolic remodeling in mice infected by the larval Echinococcus granulosus. Microarray analysis of lncRNA and mRNA reveals lipogenesis inhibition along with metabolic remodeling in mice infected by the larval Echinococcus granulosus

Parasitic infection improves metabolic homeostasis in “western diet” induced-obesity, which partially results from the regulation of adipogenesis. However, the underlying mechanism remains largely unknown. This study investigated the long non-coding RNA（lncRNA）and mRNA profiles of subcutaneous adipose tissues in mice infected by the protoscoleces of Echinococcus granulosus (EgPSC) using a microarray analysis. In comparison with control mice, the infected mice showed decreased mass of adipose tissues and shrunken size of adipocytes. The indirect calorimetry found the alternation of energy metabolism post infection, which was characterized by less CO2 production and O2 consumption, sharp decline of carbohydrate oxidation and a little increase of fat oxidation. A total of 1,052 mRNAs and 220 lncRNAs were differentially expressed in infected subcutaneous adipose tissues (fold change ≥2, P<0.05). Of them, 541 mRNAs were upregulated and 511 mRNAs were downregulated; 126 lncRNAs were upregulated and 94 lncRNAs were downregulated. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the parasitic infection reprograms a complex metabolic network. Notably, “lipoxygenase” and “Arginine and proline metabolism” pathways were significantly upregulated while “glycolysis”, “Tricarboxylic acid (TCA) cycle”, “denovo lipogenesis” and “lipid droplet” pathways were dramatically downregulated. In addition, several key lncRNAs were linked with insulin resistance and adipocyte differentiation. Overall, this study suggests that E. granulosus infection inhibits the adipogenesis, which provides a novel insight for metabolic homeostasis mediated by parasitic infection, and hypertrophic adipocytes in obesity. Overall design: Female C57BL/6J mice were intraperitoneally injected with a 200 μl suspension containing 2000 live EgPSC in 0.9% NaCl, and were sacrificed at the 16th week post infection. The lncRNA and mRNA expression patterns in subcutaneous adipose tissues of three EgPSC infected mice and three control mice were detected. The Agilent-085631 was used in this experiment and data analysis of the 6 samples were conducted by OE Biotechnology Co., Ltd., (Shanghai, China).

寄生虫感染可改善“西式饮食”诱导肥胖小鼠的代谢稳态，该效应部分源于对脂肪生成的调控。然而其潜在分子机制仍未完全阐明。本研究通过芯片分析，对细粒棘球蚴原头节（Echinococcus granulosus protoscoleces, EgPSC）感染小鼠的皮下脂肪组织长链非编码RNA（long non-coding RNA, lncRNA）和信使RNA（messenger RNA, mRNA）表达谱进行了检测。与对照组小鼠相比，感染组小鼠的脂肪组织质量降低，脂肪细胞体积缩小。间接测热法结果显示，感染后小鼠的能量代谢发生改变：二氧化碳产生量与氧气消耗量下降，碳水化合物氧化水平显著降低，而脂肪氧化水平小幅升高。感染组皮下脂肪组织中共有1052个mRNA及220个lncRNA存在差异表达（倍数变化≥2，P<0.05），其中541个mRNA上调、511个mRNA下调，126个lncRNA上调、94个lncRNA下调。基因本体论（Gene Ontology, GO）和京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路分析显示，寄生虫感染重塑了复杂的代谢调控网络。值得注意的是，“脂氧合酶”及“精氨酸与脯氨酸代谢”通路显著上调，而“糖酵解”“三羧酸（Tricarboxylic acid, TCA）循环”“从头脂肪生成”及“脂滴”通路则显著下调。此外，多个关键lncRNA与胰岛素抵抗及脂肪细胞分化相关。本研究表明，细粒棘球蚴感染可抑制脂肪生成，为解析寄生虫感染介导的代谢稳态调控以及肥胖症中的肥大脂肪细胞提供了全新视角。总体实验设计：将雌性C57BL/6J小鼠腹腔注射200μl含2000个活EgPSC的0.9%氯化钠溶液，于感染后第16周处死小鼠。对3只感染组小鼠与3只对照组小鼠的皮下脂肪组织lncRNA及mRNA表达模式进行检测。本实验采用Agilent-085631芯片平台，6份样本的数据分析由中国上海欧易生物科技有限公司（OE Biotechnology Co., Ltd., Shanghai, China）完成。