Cypess Aaron M, Cannon Barbara, Nedergaard Jan, Kazak Lawrence, Chang Douglas C, Krakoff Jonathan, Tseng Yu-Hua, Schéele Camilla, Boucher Jeremie, Petrovic Natasa, Blondin Denis P, Carpentier André C, Virtanen Kirsi A, Kooijman Sander, Rensen Patrick C N, Cero Cheryl, Kajimura Shingo
Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Cell Metab. 2025 Jan 7;37(1):12-33. doi: 10.1016/j.cmet.2024.11.002. Epub 2024 Dec 6.
Until two decades ago, brown adipose tissue (BAT) was studied primarily as a thermogenic organ of small rodents in the context of cold adaptation. The discovery of functional human BAT has opened new opportunities to understand its physiological role in energy balance and therapeutic applications for metabolic disorders. Significantly, the role of BAT extends far beyond thermogenesis, including glucose and lipid homeostasis, by releasing mediators that communicate with other cells and organs. The field has made major advances by using new model systems, ranging from subcellular studies to clinical trials, which have also led to debates. In this perspective, we identify six fundamental issues that are currently controversial and comprise dichotomous models. Each side presents supporting evidence and, critically, the necessary methods and falsifiable experiments that would resolve the dispute. With this collaborative approach, the field will continue to productively advance the understanding of BAT physiology, appreciate the importance of thermogenic adipocytes as a central area of ongoing research, and realize the therapeutic potential.
直到二十年前,棕色脂肪组织(BAT)主要是在小型啮齿动物适应寒冷的背景下作为一种产热器官进行研究。功能性人类BAT的发现为了解其在能量平衡中的生理作用以及代谢紊乱的治疗应用开辟了新的机会。值得注意的是,BAT的作用远远超出了产热,通过释放与其他细胞和器官进行交流的介质,还包括葡萄糖和脂质稳态。该领域通过使用从亚细胞研究到临床试验的新模型系统取得了重大进展,这些进展也引发了争论。从这个角度来看,我们确定了目前存在争议的六个基本问题,并构成了二分模型。双方都提供了支持证据,关键的是,还提供了解决争议所需的方法和可证伪的实验。通过这种合作方式,该领域将继续有效地推进对BAT生理学的理解,认识到产热脂肪细胞作为当前研究核心领域的重要性,并实现其治疗潜力。