The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis

Development. 2016 Mar 15;143(6):950-61. doi: 10.1242/dev.131573. Epub 2016 Feb 18.


An association between impaired fetal growth and the postnatal development of obesity has been established. Here, by comparing adipocytes differentiated from mesenchymal stem cells (MSCs) taken from the umbilical cord and derived from normal and growth-restricted neonates, we identified the transcription factor SOX6 as highly expressed only in growth-restricted individuals. We found that SOX6 regulates adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα and MEST. We further show that SOX6 interacts with β-catenin in adipocytes, suggesting an inhibition of WNT/β-catenin signaling, thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth-restricted subjects harbors hypomethylated CpGs next to SOX6 binding motifs, and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms.

Keywords: Developmental origins; Epigenetics; Fetal growth restriction; Human; Mesenchymal stem cells; Mouse; Obesity; Transcription factor; Zebrafish.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis* / drug effects
  • Adipogenesis* / genetics
  • Animals
  • Binding Sites
  • Cell Differentiation
  • CpG Islands / genetics
  • DNA Methylation / genetics
  • Down-Regulation / drug effects
  • Humans
  • Infant, Newborn
  • Infant, Small for Gestational Age / metabolism
  • Larva / drug effects
  • Lipid Metabolism / genetics
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Models, Biological
  • Obesity / genetics*
  • Oligonucleotides, Antisense / pharmacology
  • Protein Binding / drug effects
  • Proteins / genetics
  • SOXD Transcription Factors / metabolism*
  • Triglycerides / metabolism
  • Wnt Signaling Pathway / drug effects
  • Wnt Signaling Pathway / genetics
  • Zebrafish


  • Oligonucleotides, Antisense
  • Proteins
  • SOXD Transcription Factors
  • Triglycerides
  • mesoderm specific transcript protein