title: The Inhibitory Role of α2,6-Sialylation in Adipogenesis.
abstract: Adipose tissue plays critical roles in obesity and related diseases such as diabetes and cardiovascular diseases. Previous reports suggest that glycans, the most common posttranslational modifications, are involved in obesity-related diseases, but what type of glycan regulates adipogenesis during obesity remains unclear. In this study, we first quantified the mRNA levels of 167 genes (encoding 144 glycosyltransferases and 23 related enzymes) in visceral adipose tissues (VATs) from control mice and high-fat diet (HFD)-induced obese mice. We found that a gene encoding β-galactoside α2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of α2,6-linked sialic acid inN-linked glycans, was most down-regulated in VATs from obese mice. We confirmed the reduction in α2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells. Using proteomic analysis, integrin-β1 was identified as one of the target α2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding.St6gal1overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase. Furthermore,St6gal1knockout mice exhibited increased bodyweight and VAT weight after HFD feeding. The down-regulation ofSt6gal1during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation inSt6gal1silencing. Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-β1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.
authors.affiliation: From the Department of Health Science, Faculty of Sports and Health Sciences, Daito Bunka University, Higashi-Matsuyama, Saitama 355-8681, Japan and t-kabu@ic.daito.ac.jp.|the Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kaburagi
authors.affiliation: the Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Yasuhiko
authors.identifier: 0000-0002-3181-9743
authors.initials: Y
authors.lastname: Kizuka
authors.affiliation: the Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKEN, Wako, Saitama 351-0198, Japan.
authors.forename: Shinobu
authors.identifier: 0000-0003-4757-723X
authors.initials: S
authors.lastname: Kitazume
authors.affiliation: the Disease Glycomics Team, Systems Glycobiology Research Group, RIKEN-Max Planck Joint Research Center for Systems Chemical Biology, Global Research Cluster, RIKEN, Wako, Saitama 351-0198, Japan dglycotani@riken.jp.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis; D000818:Animals; D059305:Diet, High-Fat; D015536:Down-Regulation; D019012:Integrin beta1 / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000503:physiopathology; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
chemical_list: D019012:Integrin beta1; D012799:Sialyltransferases; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
keywords: DNA methylation; adipose tissue; glycosylation; glycosyltransferase; integrin-β1; obesity; β-galactoside α-2,6-sialyltransferase 1 (ST6GAL1)