Functional Inactivation of Mast Cells Enhances Subcutaneous Adipose Tissue Browning in Mice
Functional Inactivation of Mast Cells Enhances Subcutaneous Adipose Tissue Browning in Mice
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肥大细胞的功能性失活增强了小鼠皮下脂肪组织的褐变
DOI：
10.1016/j.celrep.2019.06.044
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发表时间：
2019
期刊：
影响因子：
8.8
通讯作者：
Liu Jian
中科院分区：
文献类型：
--
作者：
Zhang Xian;Wang Xin;Yin Hao;Zhang Lei;Feng Airong;Zhang Qiu-Xia;Lin Yan;Bao Bin;Hern;ez Laura L.;Shi Guo-Ping;Liu Jian
脂肪组织布朗宁和全身能量消耗提供了对抗肥胖和相关代谢疾病的防御机制。在高胆固醇西方饮食喂养的小鼠中，肥大细胞（MC）失活可改善肥胖和胰岛素抵抗，并提高代谢率，但脂肪组织MC在产热和布朗宁中的直接作用尚未得到证实。在这里，我们报告肾上腺素受体激动剂去甲肾上腺素刺激的代谢率和皮下脂肪组织（SAT）布朗宁增强MC-缺陷Kitw-sh/w-sh小鼠和MC-稳定的野生型小鼠的饲料。在Kitw-sh/w-sh小鼠中MC重建为SAT阻断了这些变化。机制研究表明，MC失活提高SAT血小板衍生生长因子受体A（PDGFRα+）脂肪细胞前体增殖，并加速米色脂肪细胞分化。使用色氨酸羟化酶1（TPH 1）抑制剂和TPH 1缺陷MC，我们表明，MC衍生的5-羟色胺抑制SAT布朗宁和全身能量消耗。在SAT中，MC功能失活或MC 5-羟色胺合成抑制促进小鼠脂肪细胞布朗宁和全身能量代谢。
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-deficientKitw-sh/w-shmice and MC-stabilized wild-type mice on a chow diet. MC reconstitution to SAT inKitw-sh/w-shmice 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.