期刊
ANNALS OF SURGERY
卷 269, 期 3, 页码 554-563出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/SLA.0000000000002465
关键词
browning; burns; hypermetabolism; macrophages; trauma
类别
资金
- National Institutes of Health [R01-GM087285-01]
- CFI Leader's Opportunity Fund [25407]
- Canadian Institutes of Health Research (CIHR) [123336]
- Vanier Canada Graduate Scholarship
- Canadian Institutes of Health Research
- Canada Fund for Innovation (CFI) Leader's Opportunity Fund Project
- National Institutes of Health
Objective: 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. Background: 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. Methods: 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. Results: 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. Conclusion: Together, our findings uncover macrophages as the key instigators and missing link in trauma-induced browning.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据