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Hypoglycemic mechanisms of Ganoderma lucidum polysaccharides F31 in db/db mice via RNA-seq and iTRAQ

Abstract

Our team has previously demonstrated that Ganoderma lucidum polysaccharides F31 showed hypoglycemic effects in diabetic mice. This study aimed to gain insight into the system-level hypoglycemic mechanisms of F31 by integrative analysis of transcriptomics and proteomics data. To explore an omics perspective to mechanisms for its action, the protein and gene expression in liver from normal control (NC), diabetic db/db control mice (DC) and F31-treated db/db mice (F31) were analyzed by iTRAQ and RNA-seq. The differential expression proteins (DEPs) and differential expression genes (DEGs) were analyzed based on their gene ontology (GO) annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and the expression of DEGs and DEPs was verified by quantitative polymerase chain reaction (qPCR) and westblotting (WB). We identified sixty-five DEGs and sixty-two DEPs in F31-treated group compared with DC. Integrated analysis of the RNA-seq data and proteomics data, we found that the two DEGs/ DEPs — Gck [glucokinase (GCK)] and Cyp4a12a [cytochrome P450, family 4, subfamily a, polypeptide 12a (CYP4A12A)] showed the same trend in mRNA and protein expression level in the comparison of F31-VS-DC. KEGG analysis revealed that peroxisome proliferator-activated receptors (PPARs) signaling pathway enriched in both of the comparisions of NC-VS-DC and F31-VS-DC at protein expression level. In analysis of gene and protein expression of candidate proteins target diabetes, we found that three genes [Gck, glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK)], three proteins [GCK, glucose transporter type 2 (GLUT2), pyruvate kinase (PYK) ] in glycolysis and gluconeogenesis pathway, protein of Janus-activated kinase 2 (JAK2) in insulin pathway, two genes [Cyp4a12a and stearoyl-CoA desaturase 2 (SCD2)] in lipid metabolism were expressed differently significantly in the F31-treated group compared with DC group,which would play the important role in the hypoglycemic acitivity of F31. Cluster analysis demonstrated that microRNAs probably participated in the regulation of genes involved the glucose metabolism. These results provides theoretical evidence for F31 as potential functional food ingredients for the prevention and treatment of type 2 diabetes.

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Publication details

The article was received on 21 Aug 2018, accepted on 05 Nov 2018 and first published on 05 Nov 2018


Article type: Paper
DOI: 10.1039/C8FO01656A
Citation: Food Funct., 2018, Accepted Manuscript
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    Hypoglycemic mechanisms of Ganoderma lucidum polysaccharides F31 in db/db mice via RNA-seq and iTRAQ

    C. Xiao, Q. Wu, Y. Xie, J. Tan, Y. Ding and L. Bai, Food Funct., 2018, Accepted Manuscript , DOI: 10.1039/C8FO01656A

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