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

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 Schön; Arne Dietrich; Min Gao; Markus Heine; Yizhi Sun; Ariana Vargas-Castillo; Susanna Søberg; Camilla Scheele; Miroslav Balaz; Matthias Blüher; Matthias Johannes Betz; Bruce M Spiegelman; Christian Wolfrum

doi:10.1016/j.cmet.2024.07.005

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

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 MoserWenfei Sun, Hua Dong, Martin Takes, Dominique Suelberg, Alexander Mameghani, Antonio Nocito, Christoph Johannes Zech, Alin Chirindel, Damian Wild, Irene A Burger, Michael R Schön, Arne Dietrich, Min Gao, Markus Heine, Yizhi Sun, Ariana Vargas-Castillo, Susanna Søberg, Camilla Scheele, Miroslav Balaz, Matthias Blüher^*, Matthias Johannes Betz^*, Bruce M Spiegelman, Christian Wolfrum^*

^*Corresponding author for this work

Schéele Group

Research output: Contribution to journal › Journal article › Research › peer-review

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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.

Original language	English
Journal	Cell Metabolism
Volume	36
Issue number	9
Pages (from-to)	2130-2145.e7
Number of pages	24
ISSN	1550-4131
DOIs	https://doi.org/10.1016/j.cmet.2024.07.005
Publication status	Published - 2024

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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., ... Wolfrum, C. (2024). Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes. Cell Metabolism, 36(9), 2130-2145.e7. https://doi.org/10.1016/j.cmet.2024.07.005

Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes. / Wang, Tongtong; Sharma, Anand Kumar; Wu, Chunyan; Maushart, Claudia Irene; Ghosh, Adhideb; Yang, Wu; Stefanicka, Patrik; Kovanicova, Zuzana; Ukropec, Jozef; Zhang, Jing; Arnold, Myrtha; Klug, Manuel; De Bock, Katrien; Schneider, Ulrich; Popescu, Cristina; Zheng, Bo; Ding, Lianggong; Long, Fen; Dewal, Revati Sumukh; Moser, Caroline; Sun, Wenfei; Dong, Hua; Takes, Martin; Suelberg, Dominique; Mameghani, Alexander; Nocito, Antonio; Zech, Christoph Johannes; Chirindel, Alin; Wild, Damian; Burger, Irene A; Schön, Michael R; Dietrich, Arne; Gao, Min; Heine, Markus; Sun, Yizhi; Vargas-Castillo, Ariana; Søberg, Susanna; Scheele, Camilla; Balaz, Miroslav; Blüher, Matthias; Betz, Matthias Johannes; Spiegelman, Bruce M; Wolfrum, Christian.

In: Cell Metabolism, Vol. 36, No. 9, 2024, p. 2130-2145.e7.

Research output: Contribution to journal › Journal article › Research › peer-review

Wang, T, Sharma, AK, Wu, C, Maushart, CI, 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, RS, Moser, C, Sun, W, Dong, H, Takes, M, Suelberg, D, Mameghani, A, Nocito, A, Zech, CJ, Chirindel, A, Wild, D, Burger, IA, Schön, MR, Dietrich, A, Gao, M, Heine, M, Sun, Y, Vargas-Castillo, A, Søberg, S, Scheele, C, Balaz, M, Blüher, M, Betz, MJ, Spiegelman, BM & Wolfrum, C 2024, 'Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes', Cell Metabolism, vol. 36, no. 9, pp. 2130-2145.e7. https://doi.org/10.1016/j.cmet.2024.07.005

Wang, Tongtong ; Sharma, Anand Kumar ; Wu, Chunyan ; Maushart, Claudia Irene ; Ghosh, Adhideb ; Yang, Wu ; Stefanicka, Patrik ; Kovanicova, Zuzana ; Ukropec, Jozef ; Zhang, Jing ; Arnold, Myrtha ; Klug, Manuel ; De Bock, Katrien ; Schneider, Ulrich ; Popescu, Cristina ; Zheng, Bo ; Ding, Lianggong ; Long, Fen ; Dewal, Revati Sumukh ; Moser, Caroline ; Sun, Wenfei ; Dong, Hua ; Takes, Martin ; Suelberg, Dominique ; Mameghani, Alexander ; Nocito, Antonio ; Zech, Christoph Johannes ; Chirindel, Alin ; Wild, Damian ; Burger, Irene A ; Schön, Michael R ; Dietrich, Arne ; Gao, Min ; Heine, Markus ; Sun, Yizhi ; Vargas-Castillo, Ariana ; Søberg, Susanna ; Scheele, Camilla ; Balaz, Miroslav ; Blüher, Matthias ; Betz, Matthias Johannes ; Spiegelman, Bruce M ; Wolfrum, Christian. / Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes. In: Cell Metabolism. 2024 ; Vol. 36, No. 9. pp. 2130-2145.e7.

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title = "Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes",

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.",

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

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doi = "10.1016/j.cmet.2024.07.005",

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T1 - Single-nucleus transcriptomics identifies separate classes of UCP1 and futile cycle adipocytes

AU - Wang, Tongtong

AU - Sharma, Anand Kumar

AU - Wu, Chunyan

AU - Maushart, Claudia Irene

AU - Ghosh, Adhideb

AU - Yang, Wu

AU - Stefanicka, Patrik

AU - Kovanicova, Zuzana

AU - Ukropec, Jozef

AU - Zhang, Jing

AU - Arnold, Myrtha

AU - Klug, Manuel

AU - De Bock, Katrien

AU - Schneider, Ulrich

AU - Popescu, Cristina

AU - Zheng, Bo

AU - Ding, Lianggong

AU - Long, Fen

AU - Dewal, Revati Sumukh

AU - Moser, Caroline

AU - Sun, Wenfei

AU - Dong, Hua

AU - Takes, Martin

AU - Suelberg, Dominique

AU - Mameghani, Alexander

AU - Nocito, Antonio

AU - Zech, Christoph Johannes

AU - Chirindel, Alin

AU - Wild, Damian

AU - Burger, Irene A

AU - Schön, Michael R

AU - Dietrich, Arne

AU - Gao, Min

AU - Heine, Markus

AU - Sun, Yizhi

AU - Vargas-Castillo, Ariana

AU - Søberg, Susanna

AU - Scheele, Camilla

AU - Balaz, Miroslav

AU - Blüher, Matthias

AU - Betz, Matthias Johannes

AU - Spiegelman, Bruce M

AU - Wolfrum, Christian

PY - 2024

Y1 - 2024

N2 - 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.

AB - 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.

U2 - 10.1016/j.cmet.2024.07.005

DO - 10.1016/j.cmet.2024.07.005

M3 - Journal article

C2 - 39084216

VL - 36

SP - 2130-2145.e7

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 9

ER -