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Haematopoietic cells produce BDNF and regulate appetite upon migration to the hypothalamus

Author

Listed:
  • Hiroshi Urabe

    (Shiga University of Medical Science
    Shiga University of Medical Science)

  • Hideto Kojima

    (Shiga University of Medical Science)

  • Lawrence Chan

    (and Molecular and Cellular Biology, Baylor College of Medicine)

  • Tomoya Terashima

    (Shiga University of Medical Science)

  • Nobuhiro Ogawa

    (Shiga University of Medical Science)

  • Miwako Katagi

    (Shiga University of Medical Science)

  • Kazunori Fujino

    (Shiga University of Medical Science)

  • Asako Kumagai

    (Shiga University of Medical Science)

  • Hiromichi Kawai

    (Shiga University of Medical Science)

  • Akihiro Asakawa

    (Kagoshima University Graduate School of Medical and Dental Sciences)

  • Akio Inui

    (Kagoshima University Graduate School of Medical and Dental Sciences)

  • Hitoshi Yasuda

    (Shiga University of Medical Science)

  • Yutaka Eguchi

    (Shiga University of Medical Science)

  • Kazuhiro Oka

    (and Molecular and Cellular Biology, Baylor College of Medicine)

  • Hiroshi Maegawa

    (Shiga University of Medical Science)

  • Atsunori Kashiwagi

    (Shiga University of Medical Science)

  • Hiroshi Kimura

    (Shiga University of Medical Science)

Abstract

Brain-derived neurotrophic factor (BDNF) suppresses food intake by acting on neurons in the hypothalamus. Here we show that BDNF-producing haematopoietic cells control appetite and energy balance by migrating to the hypothalamic paraventricular nucleus. These haematopoietic-derived paraventricular nucleus cells produce microglial markers and make direct contacts with neurons in response to feeding status. Mice with congenital BDNF deficiency, specifically in haematopoietic cells, develop hyperphagia, obesity and insulin resistance. These abnormalities are ameliorated by bone marrow transplantation with wild-type bone marrow cells. Furthermore, when injected into the third ventricle, wild-type bone marrow mononuclear cells home to the paraventricular nucleus and reverse the hyperphagia of BDNF-deficient mice. Our results suggest a novel mechanism of feeding control based on the production of BDNF by haematopoietic cells and highlight a potential new therapeutic route for the treatment of obesity.

Suggested Citation

  • Hiroshi Urabe & Hideto Kojima & Lawrence Chan & Tomoya Terashima & Nobuhiro Ogawa & Miwako Katagi & Kazunori Fujino & Asako Kumagai & Hiromichi Kawai & Akihiro Asakawa & Akio Inui & Hitoshi Yasuda & Y, 2013. "Haematopoietic cells produce BDNF and regulate appetite upon migration to the hypothalamus," Nature Communications, Nature, vol. 4(1), pages 1-10, June.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms2536
    DOI: 10.1038/ncomms2536
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