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Glycogen shortage during fasting triggers liver–brain–adipose neurocircuitry to facilitate fat utilization

Author

Listed:
  • Yoshihiko Izumida

    (Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
    Graduate School of Medicine, University of Tokyo
    Showa University School of Medicine)

  • Naoya Yahagi

    (Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
    Graduate School of Medicine, University of Tokyo
    Faculty of Medicine, University of Tsukuba)

  • Yoshinori Takeuchi

    (Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
    Faculty of Medicine, University of Tsukuba)

  • Makiko Nishi

    (Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
    Graduate School of Medicine, University of Tokyo
    Faculty of Medicine, University of Tsukuba)

  • Akito Shikama

    (Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
    Faculty of Medicine, University of Tsukuba)

  • Ayako Takarada

    (Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba)

  • Yukari Masuda

    (Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
    Graduate School of Medicine, University of Tokyo)

  • Midori Kubota

    (Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
    Graduate School of Medicine, University of Tokyo)

  • Takashi Matsuzaka

    (Faculty of Medicine, University of Tsukuba)

  • Yoshimi Nakagawa

    (Faculty of Medicine, University of Tsukuba)

  • Yoko Iizuka

    (Graduate School of Medicine, University of Tokyo)

  • Keiji Itaka

    (Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo)

  • Kazunori Kataoka

    (Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, University of Tokyo)

  • Seiji Shioda

    (Showa University School of Medicine)

  • Akira Niijima

    (Niigata University School of Medicine)

  • Tetsuya Yamada

    (Tohoku University Graduate School of Medicine)

  • Hideki Katagiri

    (Tohoku University Graduate School of Medicine)

  • Ryozo Nagai

    (Graduate School of Medicine, University of Tokyo)

  • Nobuhiro Yamada

    (Faculty of Medicine, University of Tsukuba)

  • Takashi Kadowaki

    (Graduate School of Medicine, University of Tokyo)

  • Hitoshi Shimano

    (Faculty of Medicine, University of Tsukuba)

Abstract

During fasting, animals maintain their energy balance by shifting their energy source from carbohydrates to triglycerides. However, the trigger for this switch has not yet been entirely elucidated. Here we show that a selective hepatic vagotomy slows the speed of fat consumption by attenuating sympathetic nerve-mediated lipolysis in adipose tissue. Hepatic glycogen pre-loading by the adenoviral overexpression of glycogen synthase or the transcription factor TFE3 abolished this liver–brain–adipose axis activation. Moreover, the blockade of glycogenolysis through the knockdown of the glycogen phosphorylase gene and the resulting elevation in the glycogen content abolished the lipolytic signal from the liver, indicating that glycogen is the key to triggering this neurocircuitry. These results demonstrate that liver glycogen shortage activates a liver–brain–adipose neural axis that has an important role in switching the fuel source from glycogen to triglycerides under prolonged fasting conditions.

Suggested Citation

  • Yoshihiko Izumida & Naoya Yahagi & Yoshinori Takeuchi & Makiko Nishi & Akito Shikama & Ayako Takarada & Yukari Masuda & Midori Kubota & Takashi Matsuzaka & Yoshimi Nakagawa & Yoko Iizuka & Keiji Itaka, 2013. "Glycogen shortage during fasting triggers liver–brain–adipose neurocircuitry to facilitate fat utilization," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
    • Handle: RePEc:nat:natcom:v:4:y:2013:i:1:d:10.1038_ncomms3316
    DOI: 10.1038/ncomms3316
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