Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population

Lisa Suwandhi, Irem Altun, Ruth Karlina, Viktorian Miok, Tobias Wiedemann, David Fischer, Thomas Walzthoeni, Christina Lindner, Anika Böttcher, Silke S. Heinzmann, Andreas Israel, Ahmed Elagamy Mohamed Mahmoud Khalil, Alexander Braun, Ines Pramme-Steinwachs, Ingo Burtscher, Philippe Schmitt-Kopplin, Matthias Heinig, Martin Elsner, Heiko Lickert, Fabian J. Theis and Siegfried Ussar ()
Additional contact information
Lisa Suwandhi: Institute for Diabetes and Obesity, Helmholtz Center Munich
Irem Altun: Institute for Diabetes and Obesity, Helmholtz Center Munich
Ruth Karlina: Institute for Diabetes and Obesity, Helmholtz Center Munich
Viktorian Miok: German Center for Diabetes Research (DZD)
Tobias Wiedemann: German Center for Diabetes Research (DZD)
David Fischer: Institute for Computational Biology, Helmholtz Center Munich
Thomas Walzthoeni: Institute for Computational Biology, Helmholtz Center Munich
Christina Lindner: Institute for Diabetes and Obesity, Helmholtz Center Munich
Anika Böttcher: German Center for Diabetes Research (DZD)
Silke S. Heinzmann: German Center for Diabetes Research (DZD)
Andreas Israel: Institute for Diabetes and Obesity, Helmholtz Center Munich
Ahmed Elagamy Mohamed Mahmoud Khalil: Institute for Diabetes and Obesity, Helmholtz Center Munich
Alexander Braun: Technical University of Munich
Ines Pramme-Steinwachs: Institute for Diabetes and Obesity, Helmholtz Center Munich
Ingo Burtscher: German Center for Diabetes Research (DZD)
Philippe Schmitt-Kopplin: German Center for Diabetes Research (DZD)
Matthias Heinig: Institute for Computational Biology, Helmholtz Center Munich
Martin Elsner: Technical University of Munich
Heiko Lickert: German Center for Diabetes Research (DZD)
Fabian J. Theis: Institute for Computational Biology, Helmholtz Center Munich
Siegfried Ussar: Institute for Diabetes and Obesity, Helmholtz Center Munich

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Adipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preadipocytes expressing the mature white adipocyte marker Asc-1 that showed a low ability to differentiate into beige adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preadipocytes resulted in spontaneous differentiation of beige adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preadipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine.

Date: 2021
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DOI: 10.1038/s41467-021-21826-9

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