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Wang, T.* ; Sharma, A.K.* ; Wu, C.* ; Maushart, C.I.* ; Ghosh, A.* ; Yang, W.* ; Stefanicka, P.* ; Kovanicova, Z.* ; Ukropec, J.* ; Zhang, J.* ; Arnold, M.* ; Klug, M.* ; de Bock, K.* ; Schneider, U.* ; Popescu, C.* ; Zheng, B.* ; Ding, L.* ; Long, F.* ; Dewal, R.S.* ; Moser, C.* ; Sun, W.* ; Dong, H.* ; Takes, M.* ; Suelberg, D.* ; Mameghani, A.* ; Nocito, A.* ; Zech, C.J.* ; Chirindel, A.* ; Wild, D.* ; Burger, I.A.* ; Schön, M.R.* ; Dietrich, A.* ; Gao, M.* ; Heine, M.* ; Sun, Y.* ; Vargas-Castillo, A.* ; Søberg, S.* ; Scheele, C.* ; Balaz, M.* ; Blüher, M. ; Betz, M.J.* ; Spiegelman, B.M.* ; Wolfrum, C.*

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

Cell Metab. 36, DOI: 10.1016/j.cmet.2024.07.005 (2024)

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	Open Access Gold (Paid Option)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Energy Homeostasis ; Futile Cycling ; Human Metabolism ; Single-nucleus Rna Sequencing ; Thermogenesis

ISSN (print) / ISBN 1550-4131

e-ISSN 1932-7420

Journal Cell Metabolism

Quellenangaben Volume: 36

Publisher Elsevier

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)