Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway
Tbx15 is required for adipocyte browning induced by adrenergic signaling pathway
复制标题
Tbx15 是肾上腺素信号通路诱导脂肪细胞褐变所必需的
DOI：
10.1016/j.molmet.2019.07.004
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发表时间：
2019-10-01
影响因子：
8.1
通讯作者：
Nie, Tao
中科院分区：
文献类型：
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作者：
Sun, Wei;Zhao, Xuemei;Nie, Tao
目的：T-box基因Tbx 15在脂肪组织中大量表达，尤其是皮下脂肪和棕色脂肪。虽然它的表达与肥胖相关，但其在脂肪组织中的确切生物学作用在体内知之甚少。在这里，我们调查的功能Tbx 15在棕色脂肪产热和白色脂肪布朗宁在vivo.Methods：在本研究中，我们产生了脂肪特异性Tbx 15基因敲除（AKO）小鼠通过交叉Tbx 15 floxed小鼠脂联素-Cre小鼠描绘Tbx 15在脂肪组织中的功能。我们系统地研究了Tbx 15对小鼠棕色脂肪产热和白色脂肪布朗宁的影响，以及可能的分子机制。结果：冷暴露后，Tbx 15 AKO小鼠腹股沟脂肪组织中脂肪细胞布朗宁显著受损。此外，Tbx 15的消融阻断了β 3肾上腺素能激动剂CL 316243诱导的脂肪细胞布朗宁，这似乎并没有改变Tbx 15的表达。使用染色质免疫沉淀（ChIP）的DNA结合位点分析显示，TBX 15直接结合到Prdm 16启动子的关键区域，表明它调节Prdm 16的转录，Prdm 16是脂肪细胞产热和布朗宁的主基因。与对照组小鼠相比，Tbx 15 AKO小鼠表现出增加的体重增加和降低的全身能量消耗，以响应高脂diet.Conclusion：两者合计，这些研究结果表明，Tbx 15调节脂肪细胞布朗宁，可能是一个潜在的目标，用于治疗肥胖。(C)2019年，任作家。由爱思唯尔有限公司出版。
Objective: The T-box gene Tbx15 is abundantly expressed in adipose tissues, especially subcutaneous and brown fat. Although its expression is correlated with obesity, its precise biological role in adipose tissue is poorly understood in vivo. Here we investigated the function of Tbx15 in brown adipose thermogenesis and white adipose browning in vivo.Methods: In the present study, we generated adipose-specific Tbx15 knockout (AKO) mice by crossing Tbx15 floxed mice with adiponectin-Cre mice to delineate Tbx15 function in adipose tissues. We systematically investigated the influence of Tbx15 on brown adipose thermogenesis and white adipose browning in mice, as well as the possible underlying molecular mechanism.Results: Upon cold exposure, adipocyte browning in inguinal adipose tissue was significantly impaired in Tbx15 AKO mice. Furthermore, ablation of Tbx15 blocked adipocyte browning induced by beta 3 adrenergic agonist CL 316243, which did not appear to alter the expression of Tbx15. Analysis of DNA binding sites using chromatin-immunoprecipitation (ChIP) revealed that TBX15 bound directly to a key region in the Prdm16 promoter, indicating it regulates transcription of Prdm16, the master gene for adipocyte thermogenesis and browning. Compared to control mice, Tbx15 AKO mice displayed increased body weight gain and decreased whole body energy expenditure in response to high fat diets.Conclusion: Taken together, these findings suggest that Tbx15 regulates adipocyte browning and might be a potential target for the treatment of obesity. (C) 2019 The Authors. Published by Elsevier GmbH.