Small heterodimer partner-interacting leucine zipper protein inhibits adipogenesis by regulating peroxisome proliferator-activated receptor γ activity

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Title
Small heterodimer partner-interacting leucine zipper protein inhibits adipogenesis by regulating peroxisome proliferator-activated receptor γ activity
Author(s)
Hoon Jang; Hyoung Joo Kim; Dong Hwan Kim; Jae Kyung Park; W S Sun; S Hwang; K B Oh; W G Jang; Jeong Woong Lee
Bibliographic Citation
Life Sciences, vol. 132, pp. 49-54
Publication Year
2015
Abstract
Aims: Adipocytes play a critical role in energy balance. Growth of fat tissue is achieved via an increase in adipocyte mass and the formation of newly differentiated adipocytes from precursor cells. Understanding the cellular and molecular mechanisms of adipocyte differentiation is crucial for the study of obesity- and fat-related diseases. The present study was designed to study whether small heterodimer partner-interacting leucine zipper protein (SMILE), a novel co-repressor, could regulate differentiation of adipocyte in 3T3-L1 cells. Materials and methods: Treatment of endoplasmic stress inducers, thapsigargin and tunicamycin, inhibited adipocyte differentiation, stimulated Smile mRNA expression, and repressed the expression of adiponectin (Adipoq) in 3T3-L1 pre-adipocyte. Overexpression of SMILE in 3T3-L1 cells decreased the expression of the mRNA encoding Adipoq, a major marker of adipocytes, significantly. Furthermore, knockdown of SMILE recovered the thapsigargin-mediated repression of Adipoq transcription. Co-immunoprecipitation experiments revealed that SMILE interacted physically with PPARγ in 3T3-L1 cells. In addition, chromatin immunoprecipitation experiments revealed that SMILE suppressed the binding affinity of PPARγ for the Adipoq promoter. Key findings: We demonstrate that SMILE controls adipocyte differentiation by regulating the transactivity of peroxisome proliferator-activated receptor γ (PPARγ). Significance: These findings demonstrate that SMILE represses adipocyte differentiation by regulating PPARγ transactivity; hence, SMILE is a potential regulator of PPARγ-related diseases.
Keyword
Adipocyte differentiationAdiponectinPPARγSMILE
ISSN
0024-3205
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.lfs.2015.03.021
Type
Article
Appears in Collections:
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
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