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Age-dependent Pdgfrβ signaling drives adipocyte progenitor dysfunction to alter the beige adipogenic niche in male mice

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  • Abigail M. Benvie

    (Cornell University)

  • Derek Lee

    (Cornell University)

  • Benjamin M. Steiner

    (Cornell University)

  • Siwen Xue

    (Cornell University)

  • Yuwei Jiang

    (University of Illinois at Chicago)

  • Daniel C. Berry

    (Cornell University)

Abstract

Perivascular adipocyte progenitor cells (APCs) can generate cold temperature-induced thermogenic beige adipocytes within white adipose tissue (WAT), an effect that could counteract excess fat mass and metabolic pathologies. Yet, the ability to generate beige adipocytes declines with age, creating a key challenge for their therapeutic potential. Here we show that ageing beige APCs overexpress platelet derived growth factor receptor beta (Pdgfrβ) to prevent beige adipogenesis. We show that genetically deleting Pdgfrβ, in adult male mice, restores beige adipocyte generation whereas activating Pdgfrβ in juvenile mice blocks beige fat formation. Mechanistically, we find that Stat1 phosphorylation mediates Pdgfrβ beige APC signaling to suppress IL-33 induction, which dampens immunological genes such as IL-13 and IL-5. Moreover, pharmacologically targeting Pdgfrβ signaling restores beige adipocyte development by rejuvenating the immunological niche. Thus, targeting Pdgfrβ signaling could be a strategy to restore WAT immune cell function to stimulate beige fat in adult mammals.

Suggested Citation

  • Abigail M. Benvie & Derek Lee & Benjamin M. Steiner & Siwen Xue & Yuwei Jiang & Daniel C. Berry, 2023. "Age-dependent Pdgfrβ signaling drives adipocyte progenitor dysfunction to alter the beige adipogenic niche in male mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37386-z
    DOI: 10.1038/s41467-023-37386-z
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    References listed on IDEAS

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    1. Yong Chen & Kenji Ikeda & Takeshi Yoneshiro & Annarita Scaramozza & Kazuki Tajima & Qiang Wang & Kyeongkyu Kim & Kosaku Shinoda & Carlos Henrique Sponton & Zachary Brown & Andrew Brack & Shingo Kajimu, 2019. "Thermal stress induces glycolytic beige fat formation via a myogenic state," Nature, Nature, vol. 565(7738), pages 180-185, January.
    2. Daniel C. Berry & Yuwei Jiang & Jonathan M. Graff, 2016. "Mouse strains to study cold-inducible beige progenitors and beige adipocyte formation and function," Nature Communications, Nature, vol. 7(1), pages 1-17, April.
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    Cited by:

    1. Chih-Hao Wang & Tadataka Tsuji & Li-Hong Wu & Cheng-Ying Yang & Tian Lian Huang & Mari Sato & Farnaz Shamsi & Yu-Hua Tseng, 2024. "Endothelin 3/EDNRB signaling induces thermogenic differentiation of white adipose tissue," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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