Department of Biomedical Engineering, Columbia University, New York, NY, 10027, USA.
Department of Medicine, Division of Endocrinology and Metabolism, Medical University of Vienna, A-1090, Vienna, Austria.
Sci Rep. 2018 May 21;8(1):7957. doi: 10.1038/s41598-018-25866-y.
There is widespread evidence that increasing functional mass of brown adipose tissue (BAT) via browning of white adipose tissue (WAT) could potentially counter obesity and diabetes. However, most current approaches focus on administration of pharmacological compounds which expose patients to highly undesirable side effects. Here, we describe a simple and direct tissue-grafting approach to increase BAT mass through ex vivo browning of subcutaneous WAT, followed by re-implantation into the host; this cell-therapy approach could potentially act synergistically with existing pharmacological approaches. With this process, entitled "exBAT", we identified conditions, in both mouse and human tissue, that convert whole fragments of WAT to BAT via a single step and without unwanted off-target pharmacological effects. We show that ex vivo, exBAT exhibited UCP1 immunostaining, lipid droplet formation, and mitochondrial metabolic activity consistent with native BAT. In mice, exBAT exhibited a highly durable phenotype for at least 8 weeks. Overall, these results enable a simple and scalable tissue-grafting strategy, rather than pharmacological approaches, for increasing endogenous BAT and studying its effect on host weight and metabolism.
有广泛的证据表明,通过将白色脂肪组织(WAT)褐变来增加棕色脂肪组织(BAT)的功能质量,可能有助于对抗肥胖和糖尿病。然而,目前大多数方法都集中在使用药物化合物的给药上,这些化合物会使患者产生高度不良的副作用。在这里,我们描述了一种简单直接的组织移植方法,通过体外 WAT 的褐变来增加 BAT 的质量,然后再将其重新植入宿主体内;这种细胞治疗方法可能与现有的药物治疗方法协同作用。通过这个过程,我们称之为“exBAT”,在小鼠和人体组织中确定了条件,这些条件可以通过一步转化整个 WAT 片段为 BAT,而不会产生不必要的非靶向药物作用。我们表明,体外的 exBAT 表现出 UCP1 免疫染色、脂滴形成和与天然 BAT 一致的线粒体代谢活性。在小鼠中,exBAT 至少在 8 周内表现出高度持久的表型。总的来说,这些结果为增加内源性 BAT 提供了一种简单且可扩展的组织移植策略,而不是药物治疗方法,并研究了它对宿主体重和代谢的影响。
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