PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression

Cell Rep. 2017 Sep 19;20(12):2766-2774. doi: 10.1016/j.celrep.2017.08.077.


How the nuclear receptor PPARγ regulates the development of two functionally distinct types of adipose tissue, brown and white fat, as well as the browning of white fat, remains unclear. Our previous studies suggest that PexRAP, a peroxisomal lipid synthetic enzyme, regulates PPARγ signaling and white adipogenesis. Here, we show that PexRAP is an inhibitor of brown adipocyte gene expression. PexRAP inactivation promoted adipocyte browning, increased energy expenditure, and decreased adiposity. Identification of PexRAP-interacting proteins suggests that PexRAP function extends beyond its role as a lipid synthetic enzyme. Notably, PexRAP interacts with importin-β1, a nuclear import factor, and knockdown of PexRAP in adipocytes reduced the levels of nuclear phospholipids. PexRAP also interacts with PPARγ, as well as PRDM16, a critical transcriptional regulator of thermogenesis, and disrupts the PRDM16-PPARγ complex, providing a potential mechanism for PexRAP-mediated inhibition of adipocyte browning. These results identify PexRAP as an important regulator of adipose tissue remodeling.

Keywords: PPARγ; PRDM16; UCP1; adipocyte browning; adipose tissue; beige fat; obesity.

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue, Brown / metabolism
  • Animals
  • Base Sequence
  • Cell Nucleus / metabolism
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Isotope Labeling
  • Mice, Inbred C57BL
  • Mice, Knockout
  • PPAR gamma / metabolism
  • Protein Binding
  • Protein Transport
  • Subcutaneous Fat / metabolism
  • Sugar Alcohol Dehydrogenases / genetics
  • Sugar Alcohol Dehydrogenases / metabolism*
  • Thermogenesis / genetics*
  • Transcription Factors / metabolism*
  • Transcription, Genetic


  • DNA-Binding Proteins
  • PPAR gamma
  • Prdm16 protein, mouse
  • Transcription Factors
  • PexRAP protein, mouse
  • Sugar Alcohol Dehydrogenases