Cell-autonomous activation of Hedgehog signaling inhibits brown adipose tissue development

Proc Natl Acad Sci U S A. 2015 Apr 21;112(16):5069-74. doi: 10.1073/pnas.1420978112. Epub 2015 Apr 6.


Although recent studies have shown that brown adipose tissue (BAT) arises from progenitor cells that also give rise to skeletal muscle, the developmental signals that control the formation of BAT remain largely unknown. Here, we show that brown preadipocytes possess primary cilia and can respond to Hedgehog (Hh) signaling. Furthermore, cell-autonomous activation of Hh signaling blocks early brown-preadipocyte differentiation, inhibits BAT formation in vivo, and results in replacement of neck BAT with poorly differentiated skeletal muscle. Finally, we show that Hh signaling inhibits BAT formation partially through up-regulation of chicken ovalbumin upstream promoter transcription factor II (COUP-TFII). Taken together, our studies uncover a previously unidentified role for Hh as an inhibitor of BAT development.

Keywords: Hedgehog signaling; brown adipose tissue; cell fate.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipocytes, Brown / cytology
  • Adipocytes, Brown / metabolism
  • Adipose Tissue, Brown / cytology
  • Adipose Tissue, Brown / embryology*
  • Adipose Tissue, Brown / metabolism*
  • Animals
  • COUP Transcription Factor II / metabolism
  • Cell Differentiation / genetics
  • Cilia / metabolism
  • Hedgehog Proteins / metabolism*
  • Mice
  • Signal Transduction* / genetics
  • Up-Regulation / genetics


  • COUP Transcription Factor II
  • Hedgehog Proteins