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

Asc-1 调节皮下基质细胞群中白色和米色脂肪细胞的命运

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作者: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-Koppl

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.

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