瑞士苏黎世联邦理工学院Christian Wolfrum等研究人员合作发现，单核转录组学鉴定出UCP1和无效循环脂肪细胞的不同类别。这一研究成果于2024年7月30日在线发表在国际学术期刊《细胞—代谢》上。

研究人员表示，脂肪组织可以招募利用化学能量散发热量的分解脂肪细胞。这个过程可以通过解偶联蛋白1（UCP1）进行解偶联呼吸，也可以通过利用ATP依赖性的无效循环（FC）实现。然而，这些途径如何共存仍不清楚，因为这两种过程都依赖于线粒体膜电位。

通过利用单核RNA测序解析小鼠和人类皮下脂肪组织的异质性，研究人员鉴定出至少两种不同的米色脂肪细胞亚群：FC-脂肪细胞和UCP1-米色脂肪细胞。重要的是，研究人员展示了FC-脂肪细胞亚群在代谢上高度活跃，利用FC散发能量，从而不依赖于Ucp1参与热生成。此外，FC-脂肪细胞在系统性能量稳态中起着重要作用，并与人类的葡萄糖代谢和肥胖抵抗相关联。综合来看，这些发现鉴定了一个非经典的产热脂肪细胞亚群，这可能是哺乳动物能量稳态的重要调节因子。

附：英文原文

Title: Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes

Author: Tongtong Wang, Anand Kumar Sharma, Chunyan Wu, Claudia Irene Maushart, Adhideb Ghosh, Wu Yang, Patrik Stefanicka, Zuzana Kovanicova, Jozef Ukropec, Jing Zhang, Myrtha Arnold, Manuel Klug, Katrien De Bock, Ulrich Schneider, Cristina Popescu, Bo Zheng, Lianggong Ding, Fen Long, Revati Sumukh Dewal, Caroline Moser, Wenfei Sun, Hua Dong, Martin Takes, Dominique Suelberg, Alexander Mameghani, Antonio Nocito, Christoph Johannes Zech, Alin Chirindel, Damian Wild, Irene A. Burger, Michael R. Schn, Arne Dietrich, Min Gao, Markus Heine, Yizhi Sun, Ariana Vargas-Castillo, Susanna Sberg, Camilla Scheele, Miroslav Balaz, Matthias Blüher, Matthias Johannes Betz, Bruce M. Spiegelman, Christian Wolfrum

Issue&Volume: 2024-07-30

Abstract: Adipose tissue can recruit catabolic adipocytes that utilize chemical energy to dissipate heat. This process occurs either by uncoupled respiration through uncoupling protein 1 (UCP1) or by utilizing ATP-dependent futile cycles (FCs). However, it remains unclear how these pathways coexist since both processes rely on the mitochondrial membrane potential. Utilizing single-nucleus RNA sequencing to deconvolute the heterogeneity of subcutaneous adipose tissue in mice and humans, we identify at least 2 distinct subpopulations of beige adipocytes: FC-adipocytes and UCP1-beige adipocytes. Importantly, we demonstrate that the FC-adipocyte subpopulation is highly metabolically active and utilizes FCs to dissipate energy, thus contributing to thermogenesis independent of Ucp1. Furthermore, FC-adipocytes are important drivers of systemic energy homeostasis and linked to glucose metabolism and obesity resistance in humans. Taken together, our findings identify a noncanonical thermogenic adipocyte subpopulation, which could be an important regulator of energy homeostasis in mammals.

DOI: 10.1016/j.cmet.2024.07.005

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(24)00276-6