| RRC ID |
87167
|
| 著者 |
Shi Z, Xiong S, Hu R, Wang Z, Park J, Qian Y, Wang J, Bhalla P, Velupally N, Song Q, Song Z, Jeon MS, Zhang KK, Xie L, Layden BT, Ong SG, Jiang Y.
|
| タイトル |
The Notch-PDGFRβ axis suppresses brown adipocyte progenitor differentiation in early post-natal mice.
|
| ジャーナル |
Dev Cell
|
| 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 (PDGFRβ)+ 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 PDGFRβ+ pericytes promotes brown adipogenesis by downregulating PDGFRβ. Furthermore, inhibition of Notch signaling in PDGFRβ+ 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/PDGFRβ axis negatively regulates developmental brown adipogenesis, and its repression promotes brown adipose tissue expansion and improves metabolic health.
|
| 巻・号 |
59(10)
|
| ページ |
1233-1251.e5
|
| 公開日 |
2024-5-20
|
| DOI |
10.1016/j.devcel.2024.03.012
|
| PII |
S1534-5807(24)00181-3
|
| PMID |
38569546
|
| PMC |
PMC11874136
|
| MeSH |
Adipocytes, Brown* / cytology
Adipocytes, Brown* / metabolism
Adipogenesis*
Adipose Tissue, Brown / cytology
Adipose Tissue, Brown / metabolism
Animals
Cell Differentiation*
Male
Mice
Mice, Inbred C57BL
Pericytes / cytology
Pericytes / metabolism
Receptor, Platelet-Derived Growth Factor beta* / genetics
Receptor, Platelet-Derived Growth Factor beta* / metabolism
Receptors, Notch* / metabolism
Signal Transduction
Stem Cells* / cytology
Stem Cells* / metabolism
|
| リソース情報 |
| 実験動物マウス |
RBRC01071 |
