Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland.
Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Basel and University of Basel, Basel, Switzerland.
Cell Metab. 2024 Sep 3;36(9):2130-2145.e7. doi: 10.1016/j.cmet.2024.07.005. Epub 2024 Jul 30.
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.
脂肪组织可以招募分解代谢的脂肪细胞，这些细胞利用化学能散热。这个过程要么通过解偶联蛋白 1（UCP1）的非偶联呼吸发生，要么通过利用 ATP 依赖性无效循环（FCs）发生。然而，这些途径如何共存仍不清楚，因为这两个过程都依赖于线粒体膜电位。利用单细胞 RNA 测序来剖析小鼠和人类皮下脂肪组织的异质性，我们鉴定出至少 2 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，我们证明 FC 脂肪细胞亚群具有高度代谢活性，并利用 FC 来消耗能量，从而不依赖于 Ucp1 产生生热作用。此外，FC 脂肪细胞是全身能量稳态的重要驱动因素，并与人类的葡萄糖代谢和肥胖抵抗有关。总之，我们的研究结果确定了一种非典型的产热脂肪细胞亚群，它可能是哺乳动物能量平衡的重要调节剂。
