Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-5-19
pubmed:abstractText
The accumulation of visceral adipose tissue is closely associated with insulin resistance and metabolic syndrome. Therefore, it is important to identify genes that are required for adipocyte differentiation. To identify genes that are required for the differentiation of 3T3-L1 preadipocytes into mature adipocytes, we used retrovirus insertion-mediated random mutagenesis to generate 3T3-L1 cell lines that lose their ability to differentiate into mature adipocytes. One of the genes identified was TG-interacting factor (TGIF), a DNA binding homeodomain protein that has been demonstrated to suppress Smad-mediated activation of transforming growth factor beta (TGF-beta)-regulated transcription. In the TGIF-disrupted clone of 3T3-L1 preadipocytes, the rate of differentiation into mature adipocytes was clearly reduced compared with that in the wild-type clone. Suppression of TGIF by lentivirus-mediated RNAi also inhibited the differentiation of 3T3-L1 cells. Insulin specifically increased the abundance of TGIF protein, primarily by enhancing its stability. In addition, insulin caused the rapid accumulation of TGIF in the nuclei. Forced expression of exogenous TGIF repressed both endogenous and overexpressed Smad2/3-mediated promoter activity in 3T3-L1. These findings suggest that insulin specifically antagonizes TGF-beta signaling in preadipocytes by stabilizing the putative Smad transcriptional corepressor TGIF and regulates adipocyte differentiation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1224-34
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
TG-interacting factor is required for the differentiation of preadipocytes.
pubmed:affiliation
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't