Quantitative phosphoproteomic analysis reveals the regulatory networks of elovl6 on lipid and glucose metabolism in zebrafish
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ABSTRACT: 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 the mRNA, protein and phosphorylation levels. We established the first knock-out (KO), elovl6-/-, in zebrafish. Compared with wild type (WT) zebrafish, KO presented significant higher content of whole-body lipid and lower content of fasting blood glucose. We utilized RNA-Seq, tandem mass tag (TMT) labeling-based quantitative technology, and LC-MS/MS to perform the transcriptomic, proteomic, and phosphoproteomic analyses of livers from WT and elovl6-/- zebrafish. There were 734 differentially expressed genes (DEG) and 559 differentially expressed proteins (DEP) identified out of quantifiable 47251 transcripts and 5525 proteins between elovl6-/- and WT zebrafish. Meanwhile, 680 differentially expressed phosphoproteins (DEPP) with 1054 sites were found out of quantifiable 1230 proteins with 3604 sites. GO and 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. In the phosphoproteomics, some phosphoproteins and 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 elovl6 on lipid and glucose metabolism in zebrafish. To our knowledge, this is the first multi-omic study of zebrafish lacking elovl6, which provides strong datasets to better understand many lipid/glucose metabolic risks posed to human health.
INSTRUMENT(S): Q Exactive Plus
ORGANISM(S): Danio Rerio (zebrafish) (brachydanio Rerio)
TISSUE(S): Liver
SUBMITTER: Jian Gao
LAB HEAD: Jian Gao
PROVIDER: PXD017702 | Pride | 2020-05-27
REPOSITORIES: Pride
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