Reconstruction of gene association network reveals a transmembrane protein required for adipogenesis and targeted by PPARγ

Cell Mol Life Sci. 2010 Dec;67(23):4049-64. doi: 10.1007/s00018-010-0424-5. Epub 2010 Jun 15.


We have developed a method for reconstructing gene association networks and have applied this method to gene profiles from 3T3-L1 cells. Priorization of the candidate genes pinpointed a transcript annotated as APMAP (adipocyte plasma membrane-associated protein). Functional studies showed that APMAP is upregulated in murine and human adipogenic cell models as well as in a genetic mouse model of obesity. Silencing APMAP in 3T3-L1 cells strongly impaired the differentiation into adipocytes. Moreover, APMAP expression was strongly induced by the PPARγ ligand rosiglitazone in adipocytes in vitro and in vivo in adipose tissue. Using ChIP-qPCR and luciferase reporter assays, we show a functional PPARγ binding site. In addition, we provide evidence that the extracellular C-terminal domain of APMAP is required for the function of APMAP in adipocyte differentiation. Finally, we demonstrate that APMAP translocates from the endoplasmatic reticulum to the plasma membrane during adipocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipogenesis / genetics*
  • Algorithms
  • Amino Acid Sequence
  • Animals
  • Gene Regulatory Networks*
  • Humans
  • Male
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • PPAR gamma / genetics
  • PPAR gamma / metabolism*
  • Promoter Regions, Genetic
  • RNA, Small Interfering / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment


  • APMAP protein, mouse
  • Membrane Glycoproteins
  • PPAR gamma
  • RNA, Small Interfering
  • Recombinant Fusion Proteins