Functional Inactivation of Mast Cells Enhances Subcutaneous Adipose Tissue Browning in Mice

  • Cell Rep. 2019 Jul 16;28(3):792-803.e4. doi: 10.1016/j.celrep.2019.06.044.
Xian Zhang  1 ,  Xin Wang  2 ,  Hao Yin  3 ,  Lei Zhang  2 ,  Airong Feng  3 ,  Qiu-Xia Zhang  2 ,  Yan Lin  2 ,  Bin Bao  4 ,  Laura L Hernandez  5 ,  Guo-Ping Shi  6 ,  Jian Liu  7
Affiliations
  • 1. School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • 2. School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.
  • 3. Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230026, China.
  • 4. School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei 230009, China.
  • 5. Department of Dairy Science, University of Wisconsin, Madison, WI 53706, USA.
  • 6. School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. Electronic address: [email protected].
  • 7. School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China; Engineering Research Center of Bio-process, Ministry of Education, Hefei University of Technology, Hefei 230009, China. Electronic address: [email protected].
PMID: 31315055 DOI: 10.1016/j.celrep.2019.06.044
Abstract

Adipose tissue browning and systemic energy expenditure provide a defense mechanism against obesity and associated metabolic diseases. In high-cholesterol Western diet-fed mice, mast cell (MC) inactivation ameliorates obesity and Insulin resistance and improves the metabolic rate, but a direct role of adipose tissue MCs in thermogenesis and browning remains unproven. Here, we report that adrenoceptor agonist norepinephrine-stimulated metabolic rate and subcutaneous adipose tissue (SAT) browning are enhanced in MC-deficient Kitw-sh/w-sh mice and MC-stabilized wild-type mice on a chow diet. MC reconstitution to SAT in Kitw-sh/w-sh mice blocks these changes. Mechanistic studies demonstrate that MC inactivation elevates SAT platelet-derived growth factor receptor A (PDGFRα+) adipocyte precursor proliferation and accelerates beige adipocyte differentiation. Using the Tryptophan Hydroxylase 1 (TPH1) inhibitor and TPH1-deficient MCs, we show that MC-derived serotonin inhibits SAT browning and systemic energy expenditure. Functional inactivation of MCs or inhibition of MC serotonin synthesis in SAT promotes adipocyte browning and systemic energy metabolism in mice.

Keywords
beige adipocyte; brown adipocyte; energy expenditure; mast cell; serotonin; subcutaneous adipose tissue.
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