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

Autor: Wang T; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Sharma AK; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Wu C; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Maushart CI; Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Basel and University of Basel, Basel, Switzerland., Ghosh A; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Yang W; Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China., Stefanicka P; Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine and University Hospital, Comenius University in Bratislava, Bratislava, Slovakia., Kovanicova Z; Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, Bratislava, Slovakia., Ukropec J; Institute of Experimental Endocrinology, Biomedical Research Center at the Slovak Academy of Sciences, Bratislava, Slovakia., Zhang J; Laboratory of Exercise and Health, Health Institute of Human Movement Sciences and Sport, Department of Health Sciences and Technology, ETH Zurich, Schwerzenbach, Switzerland., Arnold M; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Klug M; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., De Bock K; Laboratory of Exercise and Health, Health Institute of Human Movement Sciences and Sport, Department of Health Sciences and Technology, ETH Zurich, Schwerzenbach, Switzerland., Schneider U; Department of Surgery, Cantonal Hospital of Baden, Im Ergel 1, 5404 Baden, Switzerland., Popescu C; Department of Nuclear Medicine, Cantonal Hospital of Baden, Im Ergel 1, 5404 Baden, Switzerland., Zheng B; School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, China., Ding L; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Long F; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Dewal RS; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Moser C; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Sun W; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Dong H; Laboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, Department of Health Sciences and Technology ETH Zurich, Schwerzenbach, Switzerland., Takes M; Department of Radiology and Nuclear Medicine, University Hospital of Basel, Basel, Switzerland., Suelberg D; Department of Surgery, Cantonal Hospital of Baden, Im Ergel 1, 5404 Baden, Switzerland., Mameghani A; Department of Surgery, Cantonal Hospital of Baden, Im Ergel 1, 5404 Baden, Switzerland., Nocito A; Department of Surgery, Cantonal Hospital of Baden, Im Ergel 1, 5404 Baden, Switzerland., Zech CJ; Department of Radiology and Nuclear Medicine, University Hospital of Basel, Basel, Switzerland., Chirindel A; Department of Radiology and Nuclear Medicine, University Hospital of Basel, Basel, Switzerland., Wild D; Department of Radiology and Nuclear Medicine, University Hospital of Basel, Basel, Switzerland., Burger IA; 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., Schön MR; Städtisches Klinikum Karlsruhe, Clinic of Visceral Surgery, Karlsruhe, Germany., Dietrich A; Clinic for Visceral, Transplant and Thoracic and Vascular Surgery, University Hospital Leipzig, Liebigstrasse 20, 04103 Leipzig, Germany., Gao M; Department of Pharmacy, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China., Heine M; Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany., Sun Y; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Vargas-Castillo A; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Søberg S; 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., Scheele C; 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., Balaz M; 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., Blüher M; 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., Betz MJ; Department of Endocrinology, Diabetes, and Metabolism, University Hospital of Basel and University of Basel, Basel, Switzerland. Electronic address: matthias.betz@usb.ch., Spiegelman BM; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Cell Biology, Harvard Medical School, Boston, MA, USA., Wolfrum C; 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.
Jazyk: angličtina
Zdroj: Cell metabolism [Cell Metab] 2024 Sep 03; Vol. 36 (9), pp. 2130-2145.e7. Date of Electronic Publication: 2024 Jul 30.
DOI: 10.1016/j.cmet.2024.07.005
Abstrakt: 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.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE