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PMID: 12671681 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells.

EMBO reports ·Vol. 4 ·No. 4 ·2003-04-00 ·Pages 374-80

Shi X, Shi W, Li Q, Song B, Wan M, Bai S, Cao X

Abstract

Mesenchymal stem cells have the potential to differentiate into various cell lineages, including adipocytes and osteoblasts. The induction of adipocyte differentiation by glucocorticoids (GCs) not only causes the accumulation of fat cells in bone marrow, but also depletes the supply of osteoblasts for new bone formation, thus leading to osteoporosis. We have shown that a GC-induced leucine-zipper protein (GILZ) antagonizes adipocyte differentiation. GILZ binds to a tandem repeat of CCAAT/enhancer-binding protein (C/EBP) binding sites in the promoter of the gene encoding peroxisome-proliferator-activated receptor-gamma2 (PPAR-gamma2), and inhibits its transcription as a sequence-specific transcriptional repressor. We have also shown that ectopic expression of GILZ blocks GC-induced adipocyte differentiation. Furthermore, adipogenic marker genes (for example, those encoding PPAR-gamma2, C/EBP-alpha, lipoprotein lipase and adipsin) are also inhibited by GILZ. Our results reveal a novel GC antagonistic mechanism that has potential therapeutic applications for the inhibition of GC-induced adipocyte differentiation.

MeSH Terms
3T3 Cells Adipocytes/cytology,drug effects Animals Binding Sites CCAAT-Enhancer-Binding Proteins/metabolism Cell Differentiation/drug effects DNA-Binding Proteins/genetics Dexamethasone/pharmacology Glucocorticoids/pharmacology Leucine Zippers Mesoderm/cytology,drug effects,physiology Mice Receptors, Cytoplasmic and Nuclear/drug effects,physiology Reverse Transcriptase Polymerase Chain Reaction Transcription Factors/drug effects,genetics,physiology
Chemicals
CCAAT-Enhancer-Binding Proteins DNA-Binding Proteins Dsip1 protein, mouse Glucocorticoids Receptors, Cytoplasmic and Nuclear Transcription Factors Dexamethasone
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Shi Xingming
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. [email protected]
Shi Weibin
Li Qingnan
Song Buer
Wan Mei
Bai Shuting
Cao Xu
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1038/sj.embor.embor805
Email
[email protected]
Published
2003-04-00
Epub
2003-00-14
Pages
374-80
Language
English
Region
England
NLM ID
100963049
PMCID
PMC1319161
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.embor.embor805 PMC Full Text View journal details
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