Alternatively Activated Macrophages Drive Browning of White Adipose Tissue in Burns.
Alternatively Activated Macrophages Drive Browning of White Adipose Tissue in Burns.
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DOI：
10.1097/sla.0000000000002465
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发表时间：
2019-03
影响因子：
9
通讯作者：
Jeschke MG
中科院分区：
文献类型：
--
作者：
Abdullahi A;Auger C;Stanojcic M;Patsouris D;Parousis A;Epelman S;Jeschke MG
本研究的目的是揭示介体和机械事件，促进白色脂肪组织（WAT）响应烧伤的布朗宁。在高代谢患者（如烧伤、癌症）中，WAT的布朗宁已经提出了与恶病质、动脉粥样硬化和不良临床结局相关的实质性临床挑战。最近发现脂肪组织的布朗宁可诱导和维持高代谢。虽然布朗宁在创伤、烧伤或癌症引起的高代谢性卡顿病中起着重要作用，但其介导因素尚不清楚。WAT和血液样本采集自Sunnybrook医院Ross蒂利烧伤中心的患者。野生型、CCR 2 KO和白细胞介素（IL）-6 KO雄性小鼠购自Jax实验室，并经受30%总体表面积烧伤。通过组织学、基因表达和线粒体呼吸分析收集的WAT和血清的布朗宁标记物、巨噬细胞和代谢状态。在本研究中，我们发现烧伤诱导的布朗宁与巨噬细胞浸润增加有关，烧伤患者脂肪中2型巨噬细胞分布更大。与我们在烧伤患者中的临床发现相似，在烧伤后小鼠中也观察到巨噬细胞募集增加和2型巨噬细胞分布。负责巨噬细胞向脂肪迁移的趋化因子CCR 2的遗传丢失损害了烧伤诱导的布朗宁。从机制上讲，我们表明，巨噬细胞招募到烧伤应激皮下WAT（SWAT）进行替代激活诱导酪氨酸羟化酶的表达和儿茶酚胺的生产介导的IL-6，所需的布朗宁的SWAT的因素。总之，我们的发现揭示了巨噬细胞作为创伤诱导的布朗宁的关键煽动者和缺失环节。
The aim of this study was to uncover the mediators and mechanistic events that facilitate the browning of white adipose tissue (WAT) in response to burns. In hypermetabolic patients (eg, burns, cancer), the browning of WAT has presented substantial clinical challenges related to cachexia, atherosclerosis, and poor clinical outcomes. Browning of the adipose tissue has recently been found to induce and sustain hypermetabolism. Although browning appears central in trauma-, burn-, or cancer-induced hypermetabolic catabolism, the mediators are essentially unknown. WAT and blood samples were collected from patients admitted to the Ross Tilley Burn Centre at Sunnybrook Hospital. Wild type, CCR2 KO, and interleukin (IL)-6 KO male mice were purchased from Jax laboratories and subjected to a 30% total body surface area burn injury. WAT and serum collected were analyzed for browning markers, macrophages, and metabolic state via histology, gene expression, and mitochondrial respiration. In the present study, we show that burn-induced browning is associated with an increased macrophage infiltration, with a greater type 2 macrophage profile in the fat of burn patients. Similar to our clinical findings in burn patients, both an increase in macrophage recruitment and a type 2 macrophage profile were also observed in post burn mice. Genetic loss of the chemokine CCR2 responsible for macrophage migration to the adipose impairs burn-induced browning. Mechanistically, we show that macrophages recruited to burn-stressed subcutaneous WAT (sWAT) undergo alternative activation to induce tyrosine hydroxylase expression and catecholamine production mediated by IL-6, factors required for browning of sWAT. Together, our findings uncover macrophages as the key instigators and missing link in trauma-induced browning.