Adipose Tissue Mast Cells Promote Human Adipose Beiging in Response to Cold

Sci Rep. 2019 Jun 17;9(1):8658. doi: 10.1038/s41598-019-45136-9.

Abstract

In a recent study, repeated cold application induced beiging in subcutaneous white adipose tissue (SC WAT) of humans independent of body mass index. To identify factors that promote or inhibit beiging, we performed multiplex analysis of gene expression with the Nanostring nCounter system (the probe set contained genes for specific immune cell markers, cytokines, and chemokines) on the SC WAT from lean subjects. Multiple correlations analysis identified mast cell tryptase and CCL26, a chemokine for mast cells, as genes whose change correlated positively with the change in UCP1 in SC WAT, leading to the hypothesis that mast cells promote SC WAT beiging in response to cold. We quantified mast cell recruitment into SC WAT and degranulation. Mast cells increased in number in SC WAT in lean subjects, and there was an increase in the number of degranulated mast cells in both lean subjects and subjects with obesity. We determined that norepinephrine stimulated mast cell degranulation and histamine release in vitro. In conclusion, cold stimulated adipose tissue mast cell recruitment in lean subjects and mast cell degranulation in SC WAT of all research participants independent of baseline body mass index, suggesting that mast cells promote adipose beiging through the release of histamine or other products.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adipose Tissue, Beige / metabolism*
  • Adipose Tissue, Beige / pathology
  • Adult
  • Case-Control Studies
  • Cell Count
  • Cell Degranulation / drug effects
  • Cell Proliferation / drug effects
  • Chemokine CCL26 / genetics*
  • Chemokine CCL26 / metabolism
  • Cold Temperature
  • Cytokines / genetics
  • Cytokines / metabolism
  • Energy Metabolism / drug effects
  • Energy Metabolism / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Histamine / biosynthesis
  • Humans
  • Male
  • Mast Cells / drug effects
  • Mast Cells / metabolism*
  • Mast Cells / pathology
  • Norepinephrine / pharmacology
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / pathology
  • Subcutaneous Fat / metabolism*
  • Subcutaneous Fat / pathology
  • Thermogenesis / genetics*
  • Tryptases / genetics*
  • Tryptases / metabolism
  • Uncoupling Protein 1 / genetics
  • Uncoupling Protein 1 / metabolism

Substances

  • CCL26 protein, human
  • Chemokine CCL26
  • Cytokines
  • UCP1 protein, human
  • Uncoupling Protein 1
  • Histamine
  • Tryptases
  • Norepinephrine