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

Yoshihiko Izumida, Naoya Yahagi, Yoshinori Takeuchi, Makiko Nishi, Akito Shikama, Ayako Takarada, Yukari Masuda, Midori Kubota, Takashi Matsuzaka, Yoshimi Nakagawa, Yoko Iizuka, Keiji Itaka, Kazunori Kataoka, Seiji Shioda, Akira Niijima, Tetsuya Yamada, Hideki Katagiri, Ryozo Nagai, Nobuhiro Yamada, Takashi KadowakiHitoshi Shimano

Research output: Contribution to journalArticle

43 Citations (Scopus)

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 glycolysis 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.

Original languageEnglish
Article number2316
JournalNature communications
Volume4
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Izumida, Y., Yahagi, N., Takeuchi, Y., Nishi, M., Shikama, A., Takarada, A., Masuda, Y., Kubota, M., Matsuzaka, T., Nakagawa, Y., Iizuka, Y., Itaka, K., Kataoka, K., Shioda, S., Niijima, A., Yamada, T., Katagiri, H., Nagai, R., Yamada, N., ... Shimano, H. (2013). Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization. Nature communications, 4, [2316]. https://doi.org/10.1038/ncomms3316