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

Jingyi Chi, Zhuhao Wu, Chan Hee J. Choi, Lily Nguyen, Saba Tegegne, Sarah E. Ackerman, Audrey Crane, François Marchildon, Marc Tessier-Lavigne, Paul Cohen

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

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. Chi et al. use Adipo-Clear, a whole-tissue clearing method that permits immunolabeling and three-dimensional profiling, to identify differences in tissue architecture and sympathetic innervation between subcutaneous and visceral adipose depots. Localized beigeing of subcutaneous fat correlates with areas of dense sympathetic neurites, highlighting adipocyte regulation of the sympathetic nervous system.

Original languageEnglish
Pages (from-to)226-236.e3
JournalCell Metabolism
Volume27
Issue number1
DOIs
StatePublished - 9 Jan 2018
Externally publishedYes

Keywords

  • PRDM16
  • adipose tissue
  • beige adipocytes
  • light sheet fluorescence microscopy
  • sympathetic nervous system
  • tissue clearing

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