Functional Inactivation of Mast Cells Enhances Subcutaneous Adipose Tissue Browning in Mice
Xian Zhang,
Xin Wang,
Hao Yin,
Lei Zhang,
Airong Feng,
Qiu-Xia Zhang,
Yan Lin,
Bin Bao,
Laura L. Hernandez,
Guo-Ping Shi,
Jian Liu
Affiliations
Xian Zhang
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
Xin Wang
School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China
Hao Yin
Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230026, China
Lei Zhang
School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China
Airong Feng
Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei 230026, China
Qiu-Xia Zhang
School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China
Yan Lin
School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China
Bin Bao
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
Laura L. Hernandez
Department of Dairy Science, University of Wisconsin, Madison, WI 53706, USA
Guo-Ping Shi
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; Corresponding author
Jian Liu
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; Corresponding author
Summary: 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. : Zhang et al. report that mast cell deficiency or pharmacological inhibition in mice increases subcutaneous adipose tissue (SAT) adipocyte browning and metabolic rate by increasing SAT PDGFRα+ adipocyte precursor proliferation and beige adipocyte differentiation. Mechanistic analysis demonstrates that MC-derived serotonin inhibits SAT browning and systemic energy expenditure. Keywords: mast cell, beige adipocyte, brown adipocyte, serotonin, subcutaneous adipose tissue, energy expenditure
