snRNA-seq reveals a subpopulation of adipocytes that regulates thermogenesis

Wenfei Sun (), Hua Dong, Miroslav Balaz, Michal Slyper, Eugene Drokhlyansky, Georgia Colleluori, Antonio Giordano, Zuzana Kovanicova, Patrik Stefanicka, Lucia Balazova, Lianggong Ding, Anna Sofie Husted, Gottfried Rudofsky, Jozef Ukropec, Saverio Cinti, Thue W. Schwartz, Aviv Regev and Christian Wolfrum ()
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Wenfei Sun: Nutrition and Health, ETH Zurich
Hua Dong: Nutrition and Health, ETH Zurich
Miroslav Balaz: Nutrition and Health, ETH Zurich
Michal Slyper: Broad Institute of MIT and Harvard
Eugene Drokhlyansky: Broad Institute of MIT and Harvard
Georgia Colleluori: Marche Polytechnic University
Antonio Giordano: Marche Polytechnic University
Zuzana Kovanicova: Biomedical Research Center at the Slovak Academy of Sciences
Patrik Stefanicka: Faculty of Medicine and University Hospital, Comenius University
Lucia Balazova: Nutrition and Health, ETH Zurich
Lianggong Ding: Nutrition and Health, ETH Zurich
Anna Sofie Husted: University of Copenhagen
Gottfried Rudofsky: Cantonal Hospital Olten
Jozef Ukropec: Biomedical Research Center at the Slovak Academy of Sciences
Saverio Cinti: Marche Polytechnic University
Thue W. Schwartz: University of Copenhagen
Aviv Regev: Broad Institute of MIT and Harvard
Christian Wolfrum: Nutrition and Health, ETH Zurich

Nature, 2020, vol. 587, issue 7832, 98-102

Abstract: Abstract Adipose tissue is usually classified on the basis of its function as white, brown or beige (brite)1. It is an important regulator of systemic metabolism, as shown by the fact that dysfunctional adipose tissue in obesity leads to a variety of secondary metabolic complications2,3. In addition, adipose tissue functions as a signalling hub that regulates systemic metabolism through paracrine and endocrine signals4. Here we use single-nucleus RNA-sequencing (snRNA-seq) analysis in mice and humans to characterize adipocyte heterogeneity. We identify a rare subpopulation of adipocytes in mice that increases in abundance at higher temperatures, and we show that this subpopulation regulates the activity of neighbouring adipocytes through acetate-mediated modulation of their thermogenic capacity. Human adipose tissue contains higher numbers of cells of this subpopulation, which could explain the lower thermogenic activity of human compared to mouse adipose tissue and suggests that targeting this pathway could be used to restore thermogenic activity.

Date: 2020
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DOI: 10.1038/s41586-020-2856-x

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