Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2011-6-10
pubmed:abstractText
Angiopoietin-like protein 2 (Angptl2) is a key adipocyte-derived inflammatory mediator linking obesity to systemic insulin resistance, which is overexpressed in obesity and related metabolic diseases. However, its regulatory mechanism remains unclear. In this study, we showed that tumor necrosis factor (TNF)-? treatment increased the expression of Angptl2 gene in 3T3-L1 adipocytes. The cloning and sequence analysis of the Angptl2 gene promoter revealed the presence of several putative-binding sites for transcriptional factors, including two IREs. Insulin suppressed Angptl2 mRNA expression in dose-dependent manners, which could be attenuated by a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. The interactions between IRE sites within Angptl2 promoter and forkhead transcription factor Foxo1 were identified by EMSA and ChIP assay. Furthermore, lentivirus-mediated knockdown of Foxo1 expression inhibited the transcriptional activity of Angptl2 promoter and decreased Angptl2 mRNA expression. Finally, TNF-? inhibited Foxo1 phosphorylation and enhanced its transcriptional activity, through which TNF-? increased the expression of Angptl2 in adipocytes. These results suggest that TNF-? up-regulates Angptl2 mRNA expression via PI3K/Foxo1 pathway in 3T3-L1 adipocytes, which may be involved in obesity-induced inflammation and insulin resistance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1872-8057
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
6
pubmed:volume
339
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
120-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21501655-3T3-L1 Cells, pubmed-meshheading:21501655-5' Untranslated Regions, pubmed-meshheading:21501655-Adipocytes, pubmed-meshheading:21501655-Angiopoietins, pubmed-meshheading:21501655-Animals, pubmed-meshheading:21501655-Base Sequence, pubmed-meshheading:21501655-Cloning, Molecular, pubmed-meshheading:21501655-Forkhead Transcription Factors, pubmed-meshheading:21501655-Gene Expression, pubmed-meshheading:21501655-Gene Expression Regulation, pubmed-meshheading:21501655-HEK293 Cells, pubmed-meshheading:21501655-Humans, pubmed-meshheading:21501655-Insulin, pubmed-meshheading:21501655-Mice, pubmed-meshheading:21501655-Molecular Sequence Data, pubmed-meshheading:21501655-Response Elements, pubmed-meshheading:21501655-Sequence Analysis, DNA, pubmed-meshheading:21501655-Signal Transduction, pubmed-meshheading:21501655-Transcription, Genetic, pubmed-meshheading:21501655-Transcription Initiation Site, pubmed-meshheading:21501655-Tumor Necrosis Factor-alpha
pubmed:year
2011
pubmed:articleTitle
Tumor necrosis factor-? increases angiopoietin-like protein 2 gene expression by activating Foxo1 in 3T3-L1 adipocytes.
pubmed:affiliation
Department of Endocrinology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't