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

Autor: Anika Böttcher, Matthias Heinig, Ahmed Elagamy Mohamed Mahmoud Khalil, Lisa Suwandhi, Tobias Wiedemann, Philippe Schmitt-Kopplin, Irem Altun, Martin Elsner, Ingo Burtscher, Siegfried Ussar, Silke S. Heinzmann, David S. Fischer, Ines Pramme-Steinwachs, Viktorian Miok, Andreas Israel, Christina Lindner, Heiko Lickert, Thomas Walzthoeni, Alexander Braun, Ruth Karlina, Fabian J. Theis
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Adipocytes
White
Cell
General Physics and Astronomy
Adipose tissue
White adipose tissue
Mice
chemistry.chemical_compound
0302 clinical medicine
Adipocyte
Adipocytes
Beige
Cells
Cultured
Uncoupling Protein 1
Mice
Knockout
Mice
Inbred BALB C
education.field_of_study
Multidisciplinary
Cell Differentiation
Stromal vascular fraction
ddc
Mechanisms of disease
medicine.anatomical_structure
Differentiation
Single-Cell Analysis
Cell type
medicine.medical_specialty
Stromal cell
Amino Acid Transport System y+
Science
Adipose Tissue
White
Population
Biology
Article
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
Internal medicine
medicine
Animals
Obesity
education
Base Sequence
Sequence Analysis
RNA
General Chemistry
Adipose Tissue
Beige
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
chemistry
030217 neurology & neurosurgery
Zdroj: Nat. Commun. 12:1588 (2021)
Nature Communications
Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021)
ISSN: 2041-1723
Popis: 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.
Adipose tissue is composed of a variety of cell types, including adipocyte precursor populations, that contribute to adipose tissue function upon differentiation. Here, using scRNA-sequencing of adolescent and adult mouse subcutaneous adipose tissue, the authors identify an Asc-1 positive preadipocyte population that is enriched in adolescent subcutaneous fat and demonstrate that loss of Asc-1 triggers spontaneous beige adipocyte differentiation.
Databáze: OpenAIRE
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