The Notch-Pdgfr beta axis suppresses brown adipocyte progenitor differentiation in early postnatal mice

Shi, Z.; Xiong, S.; Hu, R.; Wang, Z.; Park, J.; Qian, Y.; Wang, J.; Bhalla, P.; Velupally, N.; Song, Q.; Song, Z.; Layden, B. T.; Jiang, Y.

doi:10.1101/2023.05.24.541839

bioRxiv · 10.1101/2023.05.24.541839

The Notch-Pdgfr beta axis suppresses brown adipocyte progenitor differentiation in early postnatal mice

Shi, Z.·Xiong, S.·Hu, R.·Wang, Z.·Park, J.·Qian, Y.·Wang, J.·Bhalla, P.·Velupally, N.·Song, Q.·Song, Z.·Layden, B. T.·Jiang, Y.

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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 studied. Here through in vivo lineage tracing, we observed that PDGFR{beta}+ pericytes give rise to developmental brown adipocytes, but not to those in adult homeostasis. In contrast, TBX18+ pericytes contribute to brown adipogenesis throughout both developmental and adult stages, though in a depot-specific manner. Mechanistically, Notch inhibition in PDGFR{beta}+ pericytes promotes brown adipogenesis through the downregulation of PDGFR{beta}. Furthermore, inhibition of Notch signaling in PDGFR{beta}+ pericytes mitigates HFHS (high-fat, high-sucrose) induced glucose and metabolic impairment in both developmental and adult stages. Collectively, these findings show that the Notch/PDGFR{beta} axis negatively regulates developmental brown adipogenesis, and its repression promotes brown adipose tissue expansion and improves metabolic health. HighlightsO_LIPDGFR{beta}+ pericytes act as an essential developmental brown APC. C_LIO_LITBX18+ pericytes contribute to brown adipogenesis in a depot-specific manner. C_LIO_LIInhibiting Notch-Pdgfr{beta} axis promotes brown APC adipogenesis. C_LIO_LIEnhanced postnatal brown adipogenesis improves metabolic health in adult stage. C_LI

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Shi, Z., Xiong, S., Hu, R., Wang, Z., Park, J., Qian, Y., Wang, J., Bhalla, P., Velupally, N., Song, Q., Song, Z., Layden, B. T., Jiang, Y.. 2023-05-24. The Notch-Pdgfr beta axis suppresses brown adipocyte progenitor differentiation in early postnatal mice. https://doi.org/10.1101/2023.05.24.541839

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