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Oestrogen signalling in white adipose progenitor cells inhibits differentiation into brown adipose and smooth muscle cells

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  • Kfir Lapid

    (University of Texas Southwestern Medical Center)

  • Ajin Lim

    (University of Texas Southwestern Medical Center)

  • Deborah J. Clegg

    (University of Texas Southwestern Medical Center)

  • Daniel Zeve

    (University of Texas Southwestern Medical Center)

  • Jonathan M. Graff

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

Abstract

Oestrogen, often via oestrogen receptor alpha (ERα) signalling, regulates metabolic physiology, highlighted by post-menopausal temperature dysregulation (hot flashes), glucose intolerance, increased appetite and reduced metabolic rate. Here we show that ERα signalling has a role in adipose lineage specification in mice. ERα regulates adipose progenitor identity and potency, promoting white adipogenic lineage commitment. White adipose progenitors lacking ERα reprogramme and enter into smooth muscle and brown adipogenic fates. Mechanistic studies highlight a TGFβ programme involved in progenitor reprogramming downstream of ERα signalling. The observed reprogramming has profound metabolic outcomes; both female and male adipose-lineage ERα-mutant mice are lean, have improved glucose sensitivity and are resistant to weight gain on a high-fat diet. Further, they are hypermetabolic, hyperphagic and hyperthermic, all consistent with a brown phenotype. Together, these findings indicate that ERα cell autonomously regulates adipose lineage commitment, brown fat and smooth muscle cell formation, and systemic metabolism, in a manner relevant to prevalent metabolic diseases.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6196
    DOI: 10.1038/ncomms6196
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    Cited by:

    1. 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.

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