RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/34310946http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/34310946http://www.w3.org/2000/01/rdf-schema#comment"Heparan sulfate (HS), a highly sulfated linear polysaccharide, is involved in diverse biological functions in various tissues. Although previous studies have suggested a possible contribution of HS to the differentiation of white adipocytes, there has been no direct evidence supporting this. Here, we inhibited the synthesis of HS chains in 3T3-L1 cells using CRISPR-Cas9 technology, resulting in impaired differentiation of adipocytes with attenuated bone morphogenetic protein 4 (BMP4)-fibroblast growth factor 1 (FGF1) signaling pathways. HS reduction resulted in reduced glucose uptake and decreased insulin-dependent intracellular signaling. We then made heterozygous mutant mice for the Ext1 gene, which encodes an enzyme essential for the HS biosynthesis, specifically in the visceral white adipose tissue (Fabp4-Cre+::Ext1flox/WT mice, hereafter called Ext1Δ/WT) to confirm the importance of HS in vivo. The expression levels of transcription factors that control adipocyte differentiation, such as peroxisome proliferator-activated receptor gamma, were reduced in Ext1Δ/WT adipocytes, which contained smaller, unilocular lipid droplets, reduced levels of enzymes involved in lipid synthesis, and altered expression of BMP4-FGF1 signaling molecules. Furthermore, we examined the impact of HS reduction in visceral white adipose tissue on systemic glucose homeostasis. We observed that Ext1Δ/WT mice showed glucose intolerance because of insulin resistance. Our results demonstrate that HS plays a crucial role in the differentiation of white adipocytes through BMP4-FGF1 signaling pathways, thereby contributing to insulin sensitivity and glucose homeostasis."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.org/dc/terms/identifier"doi:10.1016/j.jbc.2021.101006"xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/author"Mei Y."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/author"Otsuka R."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/author"Yoshikawa T."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/author"Yamaguchi Y."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/author"Morita M."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/author"Matsuzawa T."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/author"Yanai K."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/author"Irie F."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/author"Shimane A."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/pages"101006"xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/title"Heparan sulfate promotes differentiation of white adipocytes to maintain insulin sensitivity and glucose homeostasis."xsd:string
http://purl.uniprot.org/citations/34310946http://purl.uniprot.org/core/volume"297"xsd:string
http://purl.uniprot.org/citations/34310946http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/34310946
http://purl.uniprot.org/citations/34310946http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/34310946
http://purl.uniprot.org/uniprot/#_D6RE56-mappedCitation-34310946http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34310946
http://purl.uniprot.org/uniprot/#_P97464-mappedCitation-34310946http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34310946
http://purl.uniprot.org/uniprot/#_Q3V1P4-mappedCitation-34310946http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/34310946
http://purl.uniprot.org/uniprot/P97464http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/34310946
http://purl.uniprot.org/uniprot/Q3V1P4http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/34310946
http://purl.uniprot.org/uniprot/D6RE56http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/34310946