CXCL14, a Brown Adipokine that Mediates Brown-Fat-to-Macrophage Communication in Thermogenic Adaptation
CXCL14, a Brown Adipokine that Mediates Brown-Fat-to-Macrophage Communication in Thermogenic Adaptation
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DOI：
10.1016/j.cmet.2018.07.015
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发表时间：
2018-11-06
期刊：
影响因子：
29
通讯作者：
Villarroya, Francesc
中科院分区：
文献类型：
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作者：
Cereijo, Ruben;Gavalda-Navarro, Aleix;Villarroya, Francesc
棕色脂肪组织(BAT)的有益作用归因于其氧化代谢产物和产生热量的能力，但最近的数据表明，BAT的分泌特性也可能参与其中。在这里，我们确定趋化因子CXCL14(C-X-C基序趋化因子配体-14)是蝙蝠在热源激活时分泌的一种新的调节因子。我们发现，棕色脂肪细胞释放的CXCL14可以招募交替激活的(M2)巨噬细胞。暴露在寒冷中的Cxcl14基因缺失的小鼠表现出BAT活性受损，巨噬细胞募集到BAT的能力降低，主要是M2表型。CXCL14促进高脂饮食诱导的肥胖小鼠白色脂肪褐变，改善血糖/胰岛素稳态。在Stat6基因缺失的小鼠中看到的2型细胞因子信号的障碍，削弱了CXCL14的作用，促进了脂肪组织的褐变。我们认为，活性BAT是CXCL14的来源之一，CXCL14通过M2巨噬细胞募集、BAT激活和白色脂肪的褐化来促进适应性产热。
The beneficial effects of brown adipose tissue ( BAT) are attributed to its capacity to oxidize metabolites and produce heat, but recent data suggest that secretory properties of BAT may also be involved. Here, we identify the chemokine CXCL14 (C-X-C motif chemokine ligand-14) as a novel regulatory factor secreted by BAT in response to thermogenic activation. We found that the CXCL14 released by brown adipocytes recruited alternatively activated (M2) macrophages. Cxcl14-null mice exposed to cold showed impaired BAT activity and low recruitment of macrophages, mainly of the M2 phenotype, into BAT. CXCL14 promoted the browning of white fat and ameliorated glucose/insulin homeostasis in high-fat-diet-induced obese mice. Impairment of type 2 cytokine signaling, as seen in Stat6-null mice, blunts the action of CXCL14, promoting adipose tissue browning. We propose that active BAT is a source of CXCL14, which concertedly promotes adaptive thermogenesis via M2 macrophage recruitment, BAT activation, and the browning of white fat.