Commitment of adipose-resident c-kit+ progenitors to brown adipocytes contributes to adipose tissue homeostasis and remodeling
Abstract The global incidence of obesity-related metabolic disorders and their comorbidities continue to increase along with a demand for innovative therapeutic interventions. An in-depth understanding of de novo thermogenic adipogenesis is vital to harness the potential of these adipocytes. Here, w...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60754-w |
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| Summary: | Abstract The global incidence of obesity-related metabolic disorders and their comorbidities continue to increase along with a demand for innovative therapeutic interventions. An in-depth understanding of de novo thermogenic adipogenesis is vital to harness the potential of these adipocytes. Here, we combine genetic lineage tracing and single-nucleus RNA sequencing to demonstrate that adult adipose-resident c-kit+ cells are previously unidentified brown adipocyte progenitor cells (APCs). c-kit+ APCs differentiate into brown adipocytes but not white adipocytes in adipose tissue homeostasis as well as in cold exposure-, high-fat diet (HFD)- and aging-induced adipose remodeling. More importantly, the vital role of c-kit+ APCs in the generation of brown adipocytes is indicated by decreased brown fat, impaired thermogenic capacity, and excessive fat accumulation in c-kit mutant mice of both genders. In conclusion, the present study demonstrates that adult c-kit+ APCs give rise to brown adipocytes which are responsible for fat homeostasis and remodeling. Thus, c-kit+ progenitors may be an innovative and crucial target for obesity and metabolic diseases. |
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| ISSN: | 2041-1723 |