The Notch-PDGFRß axis suppresses brown adipocyte progenitor differentiation in early post-natal mice.
Dev Cell
; 59(10): 1233-1251.e5, 2024 May 20.
Article
en En
| MEDLINE
| ID: mdl-38569546
ABSTRACT
De novo brown adipogenesis holds potential in combating the epidemics of obesity and diabetes. However, the identity of brown adipocyte progenitor cells (APCs) and their regulation have not been extensively explored. Here, through in vivo lineage tracing and mouse modeling, we observed that platelet-derived growth factor receptor beta (PDGFRß)+ pericytes give rise to developmental brown adipocytes but not to those in adult homeostasis. By contrast, T-box 18 (TBX18)+ pericytes contribute to brown adipogenesis throughout both developmental and adult stages, though in a depot-specific manner. Mechanistically, Notch inhibition in PDGFRß+ pericytes promotes brown adipogenesis by downregulating PDGFRß. Furthermore, inhibition of Notch signaling in PDGFRß+ pericytes mitigates high-fat, high-sucrose (HFHS)-induced glucose and metabolic impairment in mice during their development and juvenile phases. Collectively, these findings show that the Notch/PDGFRß axis negatively regulates developmental brown adipogenesis, and its repression promotes brown adipose tissue expansion and improves metabolic health.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Células Madre
/
Diferenciación Celular
/
Receptor beta de Factor de Crecimiento Derivado de Plaquetas
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Receptores Notch
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Adipogénesis
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Adipocitos Marrones
Límite:
Animals
Idioma:
En
Revista:
Dev Cell
Asunto de la revista:
EMBRIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
Estados Unidos