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

Publication date: 16 July 2019Source: Cell Reports, Volume 28, Issue 3Author(s): Xian Zhang, Xin Wang, Hao Yin, Lei Zhang, Airong Feng, Qiu-Xia Zhang, Yan Lin, Bin Bao, Laura L. Hernandez, Guo-Ping Shi, Jian LiuSummaryAdipose 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.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research