肥大细胞功能失活增强小鼠皮下脂肪组织的棕色化。
Functional Inactivation of Mast Cells Enhances Subcutaneous Adipose Tissue Browning in Mice.
机构信息
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.
School of Food and Biological Engineering, Hefei University of Technology, Hefei 230009, China.
出版信息
Cell Rep. 2019 Jul 16;28(3):792-803.e4. doi: 10.1016/j.celrep.2019.06.044.
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 Kit mice and MC-stabilized wild-type mice on a chow diet. MC reconstitution to SAT in Kit 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.
脂肪组织棕色化和全身能量消耗为抵御肥胖症和相关代谢疾病提供了一种防御机制。在高胆固醇西方饮食喂养的小鼠中，肥大细胞（MC）失活可改善肥胖症和胰岛素抵抗，并提高代谢率，但脂肪组织 MC 在产热和棕色化中的直接作用尚未得到证实。在这里，我们报告，在 MC 缺陷 Kit 小鼠和 MC 稳定的野生型小鼠的正常饮食中，肾上腺素能激动剂去甲肾上腺素刺激代谢率和皮下脂肪组织（SAT）的棕色化增强。MC 再构成 Kit 小鼠的 SAT 可阻断这些变化。机制研究表明，MC 失活可提高 SAT 血小板衍生生长因子受体 A（PDGFRα）脂肪前体细胞的增殖，并加速米色脂肪细胞的分化。使用色氨酸羟化酶 1（TPH1）抑制剂和 TPH1 缺陷型 MC，我们表明 MC 衍生的 5-羟色胺抑制 SAT 棕色化和全身能量消耗。SAT 中 MC 的功能性失活或 MC 5-羟色胺合成的抑制可促进脂肪细胞的棕色化和小鼠的全身能量代谢。
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