美国哈佛医学院Bruce M. Spiegelman课题组发现，功能性米色脂肪细胞系的开发揭示表达UCP1和无效肌酸循环的独立亚类细胞。相关论文于2024年7月30日在线发表于国际学术期刊《细胞—代谢》。

研究人员表示，虽然解偶联蛋白1（UCP1）已被确认为脂肪热生成的主要贡献者，但最近的数据表明，替代途径，特别是无效肌酸循环（FCC），也发挥着重要作用。这些途径如何在细胞和组织中共存尚未被探索。

米色脂肪细胞生成在体内发生，但在体外建模一直困难；为此，研究人员报道了一种小鼠米色细胞系的开发，该细胞系能够执行强大的呼吸反应，包括解偶联呼吸和FCC。关键的FCC酶，即组织非特异性碱性磷酸酶（TNAP），几乎完全定位于这些细胞的线粒体中。

令人惊讶的是，从该细胞系的单细胞克隆显示，UCP1水平最高的细胞表达较少的TNAP，而TNAP表达水平最高的细胞表达较少的UCP1。对寒冷暴露小鼠的皮下脂肪进行的免疫荧光分析，证实了这些关键产热成分在不同脂肪细胞群体中的最高表达水平。

附：英文原文

Title: Development of a functional beige fat cell line uncovers independent subclasses of cells expressing UCP1 and the futile creatine cycle

Author: Ariana Vargas-Castillo, Yizhi Sun, Amanda L. Smythers, Louisa Grauvogel, Phillip A. Dumesic, Margo P. Emont, Linus T. Tsai, Evan D. Rosen, Nathan W. Zammit, Sydney M. Shaffer, Martha Ordonez, Edward T. Chouchani, Steven P. Gygi, Tongtong Wang, Anand K. Sharma, Miroslav Balaz, Christian Wolfrum, Bruce M. Spiegelman

Issue&Volume: 2024-07-30

Abstract: Although uncoupling protein 1 (UCP1) is established as a major contributor to adiposethermogenesis, recent data have illustrated an important role for alternative pathways,particularly the futile creatine cycle (FCC). How these pathways co-exist in cellsand tissues has not been explored. Beige cell adipogenesis occurs in vivo but has been difficult to model in vitro; here, we describe the development of a murine beige cell line that executes a robustrespiratory response, including uncoupled respiration and the FCC. The key FCC enzyme,tissue-nonspecific alkaline phosphatase (TNAP), is localized almost exclusively tomitochondria in these cells. Surprisingly, single-cell cloning from this cell lineshows that cells with the highest levels of UCP1 express little TNAP, and cells withthe highest expression of TNAP express little UCP1. Immunofluorescence analysis ofsubcutaneous fat from cold-exposed mice confirms that the highest levels of thesecritical thermogenic components are expressed in distinct fat cell populations.

DOI: 10.1016/j.cmet.2024.07.002

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00273-0