Integration of Metabolomics and Transcriptomics Reveals Ketone Body and Lipid Metabolism Disturbance Related to ER Stress in the Liver
Integration of Metabolomics and Transcriptomics Reveals Ketone Body and Lipid Metabolism Disturbance Related to ER Stress in the Liver
复制标题
代谢组学和转录组学的整合揭示了与肝脏内质网应激相关的酮体和脂质代谢紊乱
DOI：
10.1021/acs.jproteome.1c00167
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发表时间：
2021-07-16
影响因子：
4.4
通讯作者：
Du, Guanhua
中科院分区：
文献类型：
--
作者：
Ma, Peng;Wang, Zijing;Du, Guanhua
一旦蛋白质合成过量或错误折叠的蛋白质聚集，最终超过内质网（ER）的能力，就会达到内质网应激状态。内质网应激可影响许多组织，尤其是肝脏，其中非酒精性脂肪性肝病、肝脂肪变性等已被报道。然而，目前仍缺乏对肝脏内质网应激的系统了解，这可以通过整合组织的代谢组学和转录组学来获得。本研究利用tunicamycin诱导CS7BL/6N小鼠内质网应激。采用微阵列和非靶向代谢组学方法鉴定肝组织中显著改变的基因和代谢物。令人惊讶的是，除了可预测的未折叠蛋白反应外，肝脏脂质、精氨酸和脯氨酸代谢被证实与内质网应激有关。此外，酮体代谢在内质网应激下的变化最为显著，但鲜有研究支持。此外，琥珀酸受体1 （Sucnr1）可能是肝脏内质网应激的新标志物和治疗靶点。在本研究中，代谢组和转录组的结合为肝脏病理过程提供了可靠的信息，包括肝脏内质网应激的关键相关途径、潜在标志物和靶点。
Once protein synthesis is excessive or misfolded protein becomes aggregated, which eventually overwhelms the capacity of the endoplasmic reticulum (ER), a state named ER stress would be reached. ER stress could affect many tissues, especially the liver, in which nonalcoholic fatty liver disease, liver steatosis, etc. have been reported relative. However, there is still a lack of systematic insight into ER stress in the liver, which can be obtained by integrating metabolomics and transcriptomics of the tissue. Here, tunicamycin was utilized to induce ER stress in CS7BL/6N mice. Microarray and untargeted metabolomics were performed to identify the genes and metabolites significantly altered in liver tissues. Surprisingly, apart from the predictable unfolded protein response, liver lipid, arginine, and proline metabolisms were affirmed to be related to ER stress. Also, the ketone body metabolism changed most prominently in response to ER stress, with few studies backing. What is more, succinate receptor 1 (Sucnr1) may be a novel marker and therapeutical target of liver ER stress. In this study, the combination of the metabolome and transcriptome provided reliable information about liver pathological processes, including key relative pathways, potential markers, and targets involved in ER stress of the liver.