Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver
Abstract 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,...
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| Format: | Article |
| Language: | English |
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BMC
2019-08-01
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| Series: | Parasites & Vectors |
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| Online Access: | http://link.springer.com/article/10.1186/s13071-019-3621-6 |
| _version_ | 1811331502490779648 |
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| author | Zhi-Peng Xu Hao Chang Yang-Yue Ni Chen Li Lin Chen Min Hou Min-Jun Ji |
| author_facet | Zhi-Peng Xu Hao Chang Yang-Yue Ni Chen Li Lin Chen Min Hou Min-Jun Ji |
| author_sort | Zhi-Peng Xu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-13T16:21:30Z |
| format | Article |
| id | doaj.art-0cd3412557494d75b06fe8309fd2ff03 |
| institution | Directory Open Access Journal |
| issn | 1756-3305 |
| language | English |
| last_indexed | 2024-04-13T16:21:30Z |
| publishDate | 2019-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj.art-0cd3412557494d75b06fe8309fd2ff032022-12-22T02:39:55ZengBMCParasites & Vectors1756-33052019-08-0112111010.1186/s13071-019-3621-6Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liverZhi-Peng Xu0Hao Chang1Yang-Yue Ni2Chen Li3Lin Chen4Min Hou5Min-Jun Ji6Department of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityDepartment of Pathogen Biology, Nanjing Medical UniversityAbstract 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.http://link.springer.com/article/10.1186/s13071-019-3621-6Schistosoma japonicumMacrophagesMetabolism |
| spellingShingle | Zhi-Peng Xu Hao Chang Yang-Yue Ni Chen Li Lin Chen Min Hou Min-Jun Ji Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver Parasites & Vectors Schistosoma japonicum Macrophages Metabolism |
| title | Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver |
| title_full | Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver |
| title_fullStr | Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver |
| title_full_unstemmed | Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver |
| title_short | Schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver |
| title_sort | schistosoma japonicum infection causes a reprogramming of glycolipid metabolism in the liver |
| topic | Schistosoma japonicum Macrophages Metabolism |
| url | http://link.springer.com/article/10.1186/s13071-019-3621-6 |
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