The Inhibitory Role of ?2,6-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 ?-galactoside ?2,6-sialyltransferase-1 (St6gal1), a key enzyme responsible for the biosynthesis of ?2,6-linked sialic acid in N-linked glycans, was most down-regulated in VATs from obese mice. We confirmed the reduction in ?2,6-sialic acid in VATs from obese mice and differentiated adipocyte model 3T3-L1 cells. Using proteomic analysis, integrin-?1 was identified as one of the target ?2,6-sialylated proteins in adipose tissues, and phosphorylation of its downstream molecule focal adhesion kinase was found to be decreased after HFD feeding. St6gal1 overexpression in differentiating 3T3-L1 cells inhibited adipogenesis with increased phosphorylation of focal adhesion kinase. Furthermore, St6gal1 knockout mice exhibited increased bodyweight and VAT weight after HFD feeding. The down-regulation of St6gal1 during adipogenesis was canceled by treatment with a DNA methyltransferase inhibitor, suggesting an involvement of epigenetic DNA methylation in St6gal1 silencing. Our findings suggest that ST6GAL1 has an inhibitory role in adipogenesis through integrin-?1 activation, providing new insights into the roles and regulation mechanisms of glycans in adipocytes during obesity.

SUBMITTER: Kaburagi T 

PROVIDER: S-EPMC5313100 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature