title: Small heterodimer partner-interacting leucine zipper protein inhibits adipogenesis by regulating peroxisome proliferator-activated receptor γ activity.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  RESULTS
  We demonstrate that SMILE controls adipocyte differentiation by regulating the transactivity of peroxisome proliferator-activated receptor γ (PPARγ).
  
  
  CONCLUSIONS
  These findings demonstrate that SMILE represses adipocyte differentiation by regulating PPARγ transactivity; hence, SMILE is a potential regulator of PPARγ-related diseases.
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Functional Genomics, School of Engineering, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea.
authors.forename: Hoon
authors.initials: H
authors.lastname: Jang
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Hyoung-Joo
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Functional Genomics, School of Engineering, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea.
authors.forename: Dong-Hwan
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Park
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea.
authors.forename: Wu-Sheng
authors.initials: WS
authors.lastname: Sun
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, Republic of Korea.
authors.forename: Seongsoo
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Animal Biotechnology Division, National Institute of Animal Science, Rural Development Administration, Suwon, Republic of Korea.
authors.forename: Keon-Bong
authors.initials: KB
authors.lastname: Oh
authors.affiliation: Department of Biotechnology, School of Engineering, Daegu University, Gyeongbuk 712-714, Republic of Korea. Electronic address: jangwg@daegu.ac.kr.
authors.forename: Won-Gu
authors.initials: WG
authors.lastname: Jang
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Republic of Korea; Functional Genomics, School of Engineering, University of Science and Technology (UST), Daejeon 305-806, Republic of Korea. Electronic address: jwlee@kribb.re.kr.
authors.forename: Jeong-Woong
authors.initials: JW
authors.lastname: Lee
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects*; D052242:Adiponectin / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001391:Azo Compounds; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D051379:Mice; D047495:PPAR gamma / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001391:Azo Compounds; D050976:Basic-Leucine Zipper Transcription Factors; D017931:DNA Primers; D047495:PPAR gamma; D018160:Receptors, Cytoplasmic and Nuclear; C570109:SMILE protein, mouse; C099713:nuclear receptor subfamily 0, group B, member 2; C011049:oil red O
keywords: Adipocyte differentiation; Adiponectin; PPARγ; SMILE