Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density

Cell Metab. 2018 Jan 9;27(1):226-236.e3. doi: 10.1016/j.cmet.2017.12.011.


While the cell-intrinsic pathways governing beige adipocyte development and phenotype have been increasingly delineated, comparatively little is known about how beige adipocytes interact with other cell types in fat. Here, we introduce a whole-tissue clearing method for adipose that permits immunolabeling and three-dimensional profiling of structures including thermogenic adipocytes and sympathetic innervation. We found that tissue architecture and sympathetic innervation differ significantly between subcutaneous and visceral depots. Subcutaneous fat demonstrates prominent regional variation in beige fat biogenesis with localization of UCP1+ beige adipocytes to areas with dense sympathetic neurites. We present evidence that the density of sympathetic projections is dependent on PRDM16 in adipocytes, providing another potential mechanism underlying the metabolic benefits mediated by PRDM16. This powerful imaging tool highlights the interaction of tissue components during beige fat biogenesis and reveals a previously undescribed mode of regulation of the sympathetic nervous system by adipocytes.

Keywords: PRDM16; adipose tissue; beige adipocytes; light sheet fluorescence microscopy; sympathetic nervous system; tissue clearing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue, Beige / anatomy & histology*
  • Adipose Tissue, Beige / innervation
  • Adipose Tissue, Beige / metabolism*
  • Animals
  • DNA-Binding Proteins / metabolism*
  • Imaging, Three-Dimensional*
  • Intra-Abdominal Fat / innervation
  • Intra-Abdominal Fat / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurites / metabolism*
  • Subcutaneous Fat / innervation
  • Subcutaneous Fat / metabolism
  • Sympathetic Nervous System / metabolism*
  • Transcription Factors / metabolism*


  • DNA-Binding Proteins
  • Prdm16 protein, mouse
  • Transcription Factors