Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals

Cell Metab. 2016 Sep 13;24(3):420-433. doi: 10.1016/j.cmet.2016.08.005.


"Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels. Blocking of Cx43 channels by 18α-glycyrrhetinic acid decreases POMC-activation-induced adipose tissue beiging. Adipocyte-specific deletion of Cx43 reduces WAT beiging to a level similar to that observed in denervated fat pads. In contrast, overexpression of Cx43 is sufficient to promote beiging even with mild cold stimuli. These data reveal the importance of cell-to-cell communication, effective in cold-induced WAT beiging, for the propagation of limited neuronal inputs in adipose tissue.

Keywords: beiging; connexin 43; sympathetic signal; white adipose tissue.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptation, Physiological / drug effects
  • Adipose Tissue, Beige / drug effects
  • Adipose Tissue, Beige / metabolism*
  • Adipose Tissue, Brown / drug effects
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White / drug effects
  • Adipose Tissue, White / innervation
  • Adipose Tissue, White / metabolism*
  • Animals
  • Cold Temperature
  • Connexin 43 / metabolism*
  • Denervation
  • Gap Junctions / drug effects
  • Gap Junctions / metabolism
  • Gene Deletion
  • Glycyrrhetinic Acid / analogs & derivatives
  • Glycyrrhetinic Acid / pharmacology
  • Mice, Inbred C57BL
  • Models, Biological
  • Neurons / drug effects
  • Neurons / metabolism*
  • Promoter Regions, Genetic / genetics
  • Signal Transduction* / drug effects
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / pathology
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism


  • Connexin 43
  • Uncoupling Protein 1
  • 18alpha-glycyrrhetinic acid
  • Glycyrrhetinic Acid