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 Kadowaki and Hitoshi Shimano
Additional contact information
Yoshihiko Izumida: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
Naoya Yahagi: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
Yoshinori Takeuchi: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
Makiko Nishi: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
Akito Shikama: Nutrigenomics Research Group, 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
Midori Kubota: Nutrigenomics Research Group, Faculty of Medicine, University of Tsukuba
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

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: 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.

Date: 2013
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DOI: 10.1038/ncomms3316

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