Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of <i>Elovl6</i> on Lipid and Glucose Metabolism in Zebrafish
Elongation of very long-chain fatty acids protein 6 (Elovl6) has been reported to be associated with clinical treatments of a variety of metabolic diseases. However, there is no systematic and comprehensive study to reveal the regulatory role of Elovl6 in mRNA, protein and phosphorylation levels. We...
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| author | Xueting Wang Shouxiang Sun Xiaojuan Cao Jian Gao |
| author_facet | Xueting Wang Shouxiang Sun Xiaojuan Cao Jian Gao |
| author_sort | Xueting Wang |
| collection | DOAJ |
| description | Elongation of very long-chain fatty acids protein 6 (Elovl6) has been reported to be associated with clinical treatments of a variety of metabolic diseases. However, there is no systematic and comprehensive study to reveal the regulatory role of Elovl6 in mRNA, protein and phosphorylation levels. We established the first knock-out (KO), <i>elovl6<sup>−/−</sup></i>, in zebrafish. Compared with wild type (WT) zebrafish, KO presented significant higher whole-body lipid content and lower content of fasting blood glucose. We utilized RNA-Seq, tandem mass tag (TMT) labeling-based quantitative technology and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to perform the transcriptomic, proteomic and phosphoproteomic analyses of livers from WT and <i>elovl6<sup>−/−</sup></i> zebrafish. There were 734 differentially expressed genes (DEG) and 559 differentially expressed proteins (DEP) between <i>elovl6<sup>−/−</sup></i> and WT zebrafish, identified out of quantifiable 47251 transcripts and 5525 proteins. Meanwhile, 680 differentially expressed phosphoproteins (DEPP) with 1054 sites were found out of quantifiable 1230 proteins with 3604 sites. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis of the transcriptomic and proteomic data further suggested that the abnormal lipid metabolism and glucose metabolism in KO were mainly related to fatty acid degradation and biosynthesis, glycolysis/gluconeogenesis and PPAR signaling pathway. Based on phosphoproteomic analyses, some kinases critical for lipid metabolism and glucose metabolism, including ribosomal protein S6 kinase (Rps6kb), mitogen-activated protein kinase14 (Mapk14) and V-akt murine thymoma viral oncogene homolog 2-like (Akt2l), were identified. These results allowed us to catch on the regulatory networks of <i>elovl6</i> on lipid and glucose metabolism in zebrafish. To our knowledge, this is the first multi-omic study of zebrafish lacking <i>elovl6</i>, which provides strong datasets to better understand many lipid/glucose metabolic risks posed to human health. |
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| spelling | doaj.art-fe2091c1e62c47ecba81c08a587679f42023-11-19T22:07:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01218286010.3390/ijms21082860Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of <i>Elovl6</i> on Lipid and Glucose Metabolism in ZebrafishXueting Wang0Shouxiang Sun1Xiaojuan Cao2Jian Gao3College of Fisheries, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education/National Demonstration Center for Experimental Aquaculture Education, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education/National Demonstration Center for Experimental Aquaculture Education, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education/National Demonstration Center for Experimental Aquaculture Education, Huazhong Agricultural University, Wuhan 430070, ChinaCollege of Fisheries, Engineering Research Center of Green development for Conventional Aquatic Biological Industry in the Yangtze River Economic Belt, Ministry of Education/National Demonstration Center for Experimental Aquaculture Education, Huazhong Agricultural University, Wuhan 430070, ChinaElongation of very long-chain fatty acids protein 6 (Elovl6) has been reported to be associated with clinical treatments of a variety of metabolic diseases. However, there is no systematic and comprehensive study to reveal the regulatory role of Elovl6 in mRNA, protein and phosphorylation levels. We established the first knock-out (KO), <i>elovl6<sup>−/−</sup></i>, in zebrafish. Compared with wild type (WT) zebrafish, KO presented significant higher whole-body lipid content and lower content of fasting blood glucose. We utilized RNA-Seq, tandem mass tag (TMT) labeling-based quantitative technology and liquid chromatography-tandem mass spectrometry (LC-MS/MS) to perform the transcriptomic, proteomic and phosphoproteomic analyses of livers from WT and <i>elovl6<sup>−/−</sup></i> zebrafish. There were 734 differentially expressed genes (DEG) and 559 differentially expressed proteins (DEP) between <i>elovl6<sup>−/−</sup></i> and WT zebrafish, identified out of quantifiable 47251 transcripts and 5525 proteins. Meanwhile, 680 differentially expressed phosphoproteins (DEPP) with 1054 sites were found out of quantifiable 1230 proteins with 3604 sites. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis of the transcriptomic and proteomic data further suggested that the abnormal lipid metabolism and glucose metabolism in KO were mainly related to fatty acid degradation and biosynthesis, glycolysis/gluconeogenesis and PPAR signaling pathway. Based on phosphoproteomic analyses, some kinases critical for lipid metabolism and glucose metabolism, including ribosomal protein S6 kinase (Rps6kb), mitogen-activated protein kinase14 (Mapk14) and V-akt murine thymoma viral oncogene homolog 2-like (Akt2l), were identified. These results allowed us to catch on the regulatory networks of <i>elovl6</i> on lipid and glucose metabolism in zebrafish. To our knowledge, this is the first multi-omic study of zebrafish lacking <i>elovl6</i>, which provides strong datasets to better understand many lipid/glucose metabolic risks posed to human health.https://www.mdpi.com/1422-0067/21/8/2860zebrafish<i>elovl6</i> knockouttranscriptomicsproteomicsphosphoproteomicslipid/glucose metabolism |
| spellingShingle | Xueting Wang Shouxiang Sun Xiaojuan Cao Jian Gao Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of <i>Elovl6</i> on Lipid and Glucose Metabolism in Zebrafish International Journal of Molecular Sciences zebrafish <i>elovl6</i> knockout transcriptomics proteomics phosphoproteomics lipid/glucose metabolism |
| title | Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of <i>Elovl6</i> on Lipid and Glucose Metabolism in Zebrafish |
| title_full | Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of <i>Elovl6</i> on Lipid and Glucose Metabolism in Zebrafish |
| title_fullStr | Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of <i>Elovl6</i> on Lipid and Glucose Metabolism in Zebrafish |
| title_full_unstemmed | Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of <i>Elovl6</i> on Lipid and Glucose Metabolism in Zebrafish |
| title_short | Quantitative Phosphoproteomic Analysis Reveals the Regulatory Networks of <i>Elovl6</i> on Lipid and Glucose Metabolism in Zebrafish |
| title_sort | quantitative phosphoproteomic analysis reveals the regulatory networks of i elovl6 i on lipid and glucose metabolism in zebrafish |
| topic | zebrafish <i>elovl6</i> knockout transcriptomics proteomics phosphoproteomics lipid/glucose metabolism |
| url | https://www.mdpi.com/1422-0067/21/8/2860 |
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