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Cxcr4 regulates a pool of adipocyte progenitors and contributes to adiposity in a sex-dependent manner

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  • Benjamin M. Steiner

    (Cornell University)

  • Abigail M. Benvie

    (Cornell University)

  • Derek Lee

    (Cornell University)

  • Yuwei Jiang

    (University of Illinois at Chicago)

  • Daniel C. Berry

    (Cornell University)

Abstract

Sex steroids modulate the distribution of mammalian white adipose tissues. Moreover, WAT remodeling requires adipocyte progenitor cells. Nevertheless, the sex-dependent mechanisms regulating adipocyte progenitors remain undetermined. Here, we uncover Cxcr4 acting in a sexually dimorphic manner to affect a pool of proliferating cells leading to restriction of female fat mass. We find that deletion of Cxcr4 in Pparγ-expressing cells results in female, not male, lipodystrophy, which cannot be restored by high-fat diet consumption. Additionally, Cxcr4 deletion is associated with a loss of a pool of proliferating adipocyte progenitors. Cxcr4 loss is accompanied by the upregulation of estrogen receptor alpha in adipose-derived PPARγ-labelled cells related to estradiol hypersensitivity and stalled adipogenesis. Estrogen removal or administration of antiestrogens restores WAT accumulation and dynamics of adipose-derived cells in Cxcr4-deficient mice. These findings implicate Cxcr4 as a female adipogenic rheostat, which may inform strategies to target female adiposity.

Suggested Citation

  • Benjamin M. Steiner & Abigail M. Benvie & Derek Lee & Yuwei Jiang & Daniel C. Berry, 2024. "Cxcr4 regulates a pool of adipocyte progenitors and contributes to adiposity in a sex-dependent manner," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50985-8
    DOI: 10.1038/s41467-024-50985-8
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    References listed on IDEAS

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    1. 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.
    2. Kfir Lapid & Ajin Lim & Deborah J. Clegg & Daniel Zeve & Jonathan M. Graff, 2014. "Oestrogen signalling in white adipose progenitor cells inhibits differentiation into brown adipose and smooth muscle cells," Nature Communications, Nature, vol. 5(1), pages 1-16, December.
    3. Andrzej M. Brzozowski & Ashley C. W. Pike & Zbigniew Dauter & Roderick E. Hubbard & Tomas Bonn & Owe Engström & Lars Öhman & Geoffrey L. Greene & Jan-Åke Gustafsson & Mats Carlquist, 1997. "Molecular basis of agonism and antagonism in the oestrogen receptor," Nature, Nature, vol. 389(6652), pages 753-758, October.
    4. Yuwei Jiang & Daniel C. Berry & Ayoung Jo & Wei Tang & Robert W. Arpke & Michael Kyba & Jonathan M. Graff, 2017. "A PPARγ transcriptional cascade directs adipose progenitor cell-niche interaction and niche expansion," Nature Communications, Nature, vol. 8(1), pages 1-16, August.
    5. Margo P. Emont & Christopher Jacobs & Adam L. Essene & Deepti Pant & Danielle Tenen & Georgia Colleluori & Angelica Vincenzo & Anja M. Jørgensen & Hesam Dashti & Adam Stefek & Elizabeth McGonagle & So, 2022. "A single-cell atlas of human and mouse white adipose tissue," Nature, Nature, vol. 603(7903), pages 926-933, March.
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