Stimulation of histamine H4 receptor participates in cold-induced browning of subcutaneous white adipose tissue
Stimulation of histamine H4 receptor participates in cold-induced browning of subcutaneous white adipose tissue
复制标题
组胺 H4 受体的刺激参与冷诱导的皮下白色脂肪组织褐变
DOI：
10.1152/ajpendo.00131.2019
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发表时间：
2019-12-01
影响因子：
5.1
通讯作者：
Qian, Shu-wen
中科院分区：
文献类型：
--
作者：
Zhao, Ya-xin;Pan, Jia-bao;Qian, Shu-wen
虽然许多研究表明组胺及其信号通过中枢神经系统调节能量稳态，但它们在脂肪组织中的作用仍然知之甚少。在这里，我们鉴定了组胺H4受体（HrH 4）在脂肪细胞中以高于其他三种受体的水平高度表达（即，HrH 1、HrH 2和HrH 3）。HrH 4在脂肪细胞中的表达通过产热和脂解对冷作出反应，这得到了小鼠和细胞模型结果的支持。当皮下白色脂肪组织（scWAT）中的HrH 4表达被敲低时，由冷引发的布朗宁和脂解作用被消除，并且在正常和冷条件下的耗氧量也降低。此外，当4-甲基组胺（4 MH），一种选择性的HrH 4激动剂，小鼠表现出棕色的scWAT，加速的代谢率，并耐受低温。被注射到scWAT附近。与这些发现一致，4 MH也引发培养的C3 H 10 T1/2脂肪细胞的布朗宁和脂解作用。在机制上，我们证明p38/MAPK和ERK/MAPK通路参与了这些过程。总之，我们的发现揭示了HrH 4在脂肪组织布朗宁中的有效作用。
Although many studies have shown that histamine and its signaling regulate energy homeostasis through the central nervous system, their roles in adipose tissues remain poorly understood. Here, we identified that the histamine H4 receptor (HrH4) was highly expressed in adipocytes at a level higher than that of the other three receptors (i.e., HrH1, HrH2, and HrH3). The HrH4 expression in adipocytes responded to cold through thermogenesis and lipolysis, supported by results from both mouse and cell models. When HrH4 expression was knocked down in the subcutaneous white adipose tissue (scWAT), browning and lipolysis effects triggered by cold were ablated, and the oxygen consumption was also lowered both at the normal and cold conditions. Moreover, mice exhibited browned scWAT, accelerated metabolic rates, and tolerance to hypothermia when 4-methylhistamine (4MH), a selective HrH4 agonist. was adjacently injected to the scWAT. Consistent with these findings, 4MH also triggered the browning and lipolytic effects in cultured C3H10T1/2 adipocytes. Mechanically, we demonstrated that p38/MAPK and ERK/MAPK pathways were involved in these processes. In conclusion, our findings have uncovered an effective role of HrH4 in adipose tissue browning.