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

Life Sci. 2015 Jul 1:132:49-54. doi: 10.1016/j.lfs.2015.03.021. Epub 2015 Apr 18.

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.

Keywords: Adipocyte differentiation; Adiponectin; PPARγ; SMILE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / cytology
  • Adipocytes / drug effects*
  • Adipogenesis / drug effects*
  • Adiponectin / antagonists & inhibitors
  • Adiponectin / metabolism
  • Animals
  • Azo Compounds
  • Basic-Leucine Zipper Transcription Factors / genetics
  • Basic-Leucine Zipper Transcription Factors / metabolism
  • Basic-Leucine Zipper Transcription Factors / pharmacology*
  • Blotting, Western
  • Cell Differentiation / drug effects*
  • Chromatin Immunoprecipitation
  • DNA Primers / genetics
  • Gene Knockdown Techniques
  • Genetic Vectors / genetics
  • Mice
  • PPAR gamma / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • Adiponectin
  • Adipoq protein, mouse
  • Azo Compounds
  • Basic-Leucine Zipper Transcription Factors
  • DNA Primers
  • PPAR gamma
  • Receptors, Cytoplasmic and Nuclear
  • SMILE protein, mouse
  • nuclear receptor subfamily 0, group B, member 2
  • oil red O