2. Academic Validation
  3. Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes

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

  • Cell Metab. 2024 Jul 26:S1550-4131(24)00276-6. doi: 10.1016/j.cmet.2024.07.005.
Tongtong Wang 1,  Anand Kumar Sharma 1,  Chunyan Wu 1,  Claudia Irene Maushart 2,  Adhideb Ghosh 1,  Wu Yang 3,  Patrik Stefanicka 4,  Zuzana Kovanicova 5,  Jozef Ukropec 5,  Jing Zhang 6,  Myrtha Arnold 1,  Manuel Klug 1,  Katrien De Bock 6,  Ulrich Schneider 7,  Cristina Popescu 8,  Bo Zheng 9,  Lianggong Ding 1,  Fen Long 1,  Revati Sumukh Dewal 1,  Caroline Moser 1,  Wenfei Sun 1,  Hua Dong 1,  Martin Takes 10,  Dominique Suelberg 7,  Alexander Mameghani 7,  Antonio Nocito 7,  Christoph Johannes Zech 10,  Alin Chirindel 10,  Damian Wild 10,  Irene A Burger 11,  Michael R Schön 12,  Arne Dietrich 13,  Min Gao 14,  Markus Heine 15,  Yizhi Sun 16,  Ariana Vargas-Castillo 16,  Susanna Søberg 17,  Camilla Scheele 17,  Miroslav Balaz 18,  Matthias Blüher 19,  Matthias Johannes Betz 20,  Bruce M Spiegelman 16,  Christian Wolfrum 21
Affiliations

Affiliations

  • 1 Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland.
  • 2 Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Basel and University of Basel, Basel, Switzerland.
  • 3 Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.
  • 4 Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University in Bratislava, Bratislava, Slovakia.
  • 5 Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, Bratislava, Slovakia.
  • 6 Laboratory of Exercise and Health, Health Institute of Human Movement Sciences and Sport, Department of Health Sciences and Technology, ETH Zurich, Schwerzenbach, Switzerland.
  • 7 Department of Surgery, Cantonal Hospital of Baden, Im Ergel 1, 5404 Baden, Switzerland.
  • 8 Department of Nuclear Medicine, Cantonal Hospital of Baden, Im Ergel 1, 5404 Baden, Switzerland.
  • 9 School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China.
  • 10 Department of Radiology and Nuclear Medicine, University Hospital of Basel, Basel, Switzerland.
  • 11 Department of Nuclear Medicine, Cantonal Hospital of Baden, Im Ergel 1, 5404 Baden, Switzerland; Department of Nuclear Medicine, University Hospital of Zurich, University of Zurich, Zurich, Switzerland.
  • 12 Städtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, Karlsruhe, Germany.
  • 13 Clinic for Visceral, Transplant and Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany.
  • 14 Department of Pharmacy, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
  • 15 Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.
  • 16 Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
  • 17 Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, 2200 Copenhagen, Denmark; The Center of Inflammation and Metabolism and the Center for Physical Activity Research, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark.
  • 18 Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, Bratislava, Slovakia; Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University in Bratislava, Bratislava, Slovakia.
  • 19 Medical Department III - Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Germany & Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital, Leipzig, Germany. Electronic address: matthias.blueher@medizin.uni-leipzig.de.
  • 20 Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Basel and University of Basel, Basel, Switzerland. Electronic address: matthias.betz@usb.ch.
  • 21 Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland. Electronic address: christian-wolfrum@ethz.ch.
PMID: 39084216 DOI: 10.1016/j.cmet.2024.07.005
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.

Keywords

energy homeostasis; futile cycling; human metabolism; single-nucleus RNA sequencing; thermogenesis.

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