Amplification of Adipogenic Commitment by VSTM2A

Cell Rep. 2017 Jan 3;18(1):93-106. doi: 10.1016/j.celrep.2016.12.015.

Abstract

Despite progress in our comprehension of the mechanisms regulating adipose tissue development, the nature of the factors that functionally characterize adipose precursors is still elusive. Defining the early steps regulating adipocyte development is needed for the generation of tools to control adipose tissue size and function. Here, we report the discovery of V-set and transmembrane domain containing 2A (VSTM2A) as a protein expressed and secreted by committed preadipocytes. VSTM2A expression is elevated in the early phases of adipogenesis in vitro and adipose tissue development in vivo. We show that VSTM2A-producing cells associate with the vasculature and express the common surface markers of adipocyte progenitors. Overexpression of VSTM2A induces adipogenesis, whereas its depletion impairs this process. VSTM2A controls preadipocyte determination at least in part by modulating BMP signaling and PPARγ2 activation. We propose a model in which VSTM2A is produced to preserve and amplify the adipogenic capability of adipose precursors.

Keywords: 3T3-L1; adipogenesis; adipogenic commitment; adipose tissue; cell differentiation; cell signaling; obesity; preadipocyte.

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipogenesis*
  • Adipose Tissue, White / blood supply
  • Adipose Tissue, White / cytology
  • Animals
  • Biomarkers / metabolism
  • Bone Morphogenetic Proteins / metabolism
  • Cell Differentiation
  • Cell Lineage*
  • Gene Knockdown Techniques
  • Humans
  • Male
  • Membrane Proteins / metabolism*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • NIH 3T3 Cells
  • Neovascularization, Physiologic
  • PPAR gamma / metabolism
  • Receptors, Immunologic / metabolism*
  • Signal Transduction

Substances

  • Biomarkers
  • Bone Morphogenetic Proteins
  • Membrane Proteins
  • PPAR gamma
  • Receptors, Immunologic
  • VSTM2 protein, mouse
  • VSTM2A protein, human