Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease
Liver disorder often occurs in patients with inflammatory bowel disease (IBD); however, the changes in IBD-induced liver disorder at the intrinsic molecular level (chiefly metabolites) and therapeutic targets are still poorly characterized. First, a refined and translationally relevant model of DSS...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2020/6020247 |
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| author | Zhongquan Xin Zhenya Zhai Hongrong Long Fan Zhang Xiaojun Ni Jinping Deng Lunzhao Yi Baichuan Deng |
| author_facet | Zhongquan Xin Zhenya Zhai Hongrong Long Fan Zhang Xiaojun Ni Jinping Deng Lunzhao Yi Baichuan Deng |
| author_sort | Zhongquan Xin |
| collection | DOAJ |
| description | Liver disorder often occurs in patients with inflammatory bowel disease (IBD); however, the changes in IBD-induced liver disorder at the intrinsic molecular level (chiefly metabolites) and therapeutic targets are still poorly characterized. First, a refined and translationally relevant model of DSS chronic colitis in C57BL/6 mice was established, and cecropin A and antibiotics were used as interventions. We found that the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the liver tissues of mice were highly increased in the context of DSS treatment but were lowered by cecropin A and antibiotics. Subsequently, an untargeted metabolomics analysis was performed by UPLC–Orbitrap–MS/MS to reveal the metabolic profile and attempt to find the potential therapeutic targets of the liver disorders that occur in IBD. Notably, 133 metabolites were identified by an integrated database. Metabolism network and pathway analyses demonstrated that the metabolic disturbance of the liver in IBD mice was mainly enriched in bile acid metabolism, arachidonic acid metabolism, amino acid metabolism, and steroid hormone biosynthesis, while those disturbances were regulated or reversed through cecropin A and antibiotic treatment. Furthermore, the top 20 metabolites, such as glutathione, maltose, arachidonic acid, and thiamine, were screened as biomarkers via one-way analysis of variance (one-way ANOVA, p<0.05) coupled with variable importance for project values (VIP >1) of orthogonal partial least-squares discriminant analysis (OPLS-DA), which could be upregulated or downregulated with the cecropin A and antibiotics treatment. Spearman correlation analysis showed that the majority of the biomarkers have a significant correlation with cytokines (TNF-α, IL-1β, IL-6, and IL-10), indicating that those biomarkers may act as potential targets to interact directly or indirectly with cecropin A and antibiotics to affect liver inflammation. Collectively, our results extend the understanding of the molecular alteration of liver disorders occurring in IBD and offer an opportunity for discovering potential therapeutic targets in the IBD process. |
| format | Article |
| id | doaj-art-41eb55d2e0104906a32760dd83c013a5 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-41eb55d2e0104906a32760dd83c013a52025-02-03T01:05:07ZengWileyMediators of Inflammation0962-93511466-18612020-01-01202010.1155/2020/60202476020247Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel DiseaseZhongquan Xin0Zhenya Zhai1Hongrong Long2Fan Zhang3Xiaojun Ni4Jinping Deng5Lunzhao Yi6Baichuan Deng7Maoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaInstitute of Biological Resource, Jiangxi Academy of Sciences, Nanchang 330029, ChinaMaoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaMaoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaYunnan Animal Science and Veterinary Institute, Jindian, Panlong County, Kunming City, Yunnan Province, ChinaMaoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaYunnan Food Safety Research Institute, Kunming University of Science and Technology, Kunming 650500, ChinaMaoming Branch, Guangdong Laboratory for Lingnan Modern Agriculture, Guangdong Provincial Key Laboratory of Animal Nutrition Control, National Engineering Research Center for Breeding Swine Industry, College of Animal Science, South China Agricultural University, Guangzhou, ChinaLiver disorder often occurs in patients with inflammatory bowel disease (IBD); however, the changes in IBD-induced liver disorder at the intrinsic molecular level (chiefly metabolites) and therapeutic targets are still poorly characterized. First, a refined and translationally relevant model of DSS chronic colitis in C57BL/6 mice was established, and cecropin A and antibiotics were used as interventions. We found that the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in the liver tissues of mice were highly increased in the context of DSS treatment but were lowered by cecropin A and antibiotics. Subsequently, an untargeted metabolomics analysis was performed by UPLC–Orbitrap–MS/MS to reveal the metabolic profile and attempt to find the potential therapeutic targets of the liver disorders that occur in IBD. Notably, 133 metabolites were identified by an integrated database. Metabolism network and pathway analyses demonstrated that the metabolic disturbance of the liver in IBD mice was mainly enriched in bile acid metabolism, arachidonic acid metabolism, amino acid metabolism, and steroid hormone biosynthesis, while those disturbances were regulated or reversed through cecropin A and antibiotic treatment. Furthermore, the top 20 metabolites, such as glutathione, maltose, arachidonic acid, and thiamine, were screened as biomarkers via one-way analysis of variance (one-way ANOVA, p<0.05) coupled with variable importance for project values (VIP >1) of orthogonal partial least-squares discriminant analysis (OPLS-DA), which could be upregulated or downregulated with the cecropin A and antibiotics treatment. Spearman correlation analysis showed that the majority of the biomarkers have a significant correlation with cytokines (TNF-α, IL-1β, IL-6, and IL-10), indicating that those biomarkers may act as potential targets to interact directly or indirectly with cecropin A and antibiotics to affect liver inflammation. Collectively, our results extend the understanding of the molecular alteration of liver disorders occurring in IBD and offer an opportunity for discovering potential therapeutic targets in the IBD process.http://dx.doi.org/10.1155/2020/6020247 |
| spellingShingle | Zhongquan Xin Zhenya Zhai Hongrong Long Fan Zhang Xiaojun Ni Jinping Deng Lunzhao Yi Baichuan Deng Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease Mediators of Inflammation |
| title | Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease |
| title_full | Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease |
| title_fullStr | Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease |
| title_full_unstemmed | Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease |
| title_short | Metabolic Profiling by UPLC–Orbitrap–MS/MS of Liver from C57BL/6 Mice with DSS-Induced Inflammatory Bowel Disease |
| title_sort | metabolic profiling by uplc orbitrap ms ms of liver from c57bl 6 mice with dss induced inflammatory bowel disease |
| url | http://dx.doi.org/10.1155/2020/6020247 |
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