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

• Project/Area Number: 25461332
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: IZUMIDA YOSHIHIKO 東京大学, 医学部附属病院, 助教 (80384410)
• Co-Investigator(Kenkyū-buntansha): Yahagi Naoya 筑波大学, 医学医療系, 准教授 (60420246)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 糖・脂質代謝 / 神経 / グリコーゲン / 代謝 / 肝臓 / 生体情報 / 神経伝達物質 / ＧＰＣＲ / Metabolism / Neuronal informatics / Lipolysis / Obesity

Outline of Final Research Achievements

During fasting, animals maintain their energy balance by shifting their energy source from carbohydrates to triglycerides. 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 [corrected] 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.

Research Products

• [Journal Article] Autonomic nervous system-mediated effects of galanin-like peptide on lipid metabolism in liver and adipose tissue. (2016)
  • Author(s): HirakoS, Wada N, Kageyama H, Takenoya F , Izumida Y, Kim H, IizukaY, Matsumoto A, Okabe M, Kimura A, Suzuki M, Yamanaka S, Shioda S.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 1-9
  • DOI: 10.1038/srep21481
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of human ELOVL5 enhancer regions controlled by SREBP. (2015)
  • Author(s): Shikama A, Shinozaki H, Takeuchi Y, Matsuzaka T, Aita Y, Murayama T, Sawada Y, Piao X, Toya N, Oya Y, Takarada A, Masuda Y, Nishi M, Kubota M, Izumida Y, Nakagawa Y, Iwasaki H, Kobayashi K, Yatoh S, Suzuki H, Yagyu H, Kawakami Y, Yamada N, Shimano H, Yahagi N.
  • Journal Title: Biochem Biophys Res Commun. Volume: 465(4) Issue: 4 Pages: 857-63
  • DOI: 10.1016/j.bbrc.2015.08.101
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization. (2013)
  • Author(s): 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, Kadowaki T, Shimano H
  • Journal Title: Nat Commun. Volume: 4 Issue: 1 Pages: 2316-2316
  • DOI: 10.1038/ncomms3316
  • Peer Reviewed / Open Access
• [Presentation] 糖と脂質－神経によるエネルギー供給源の新たなスイッチング・メカニズム (2014)
  • Author(s): 泉田欣彦 矢作直也 武内謙憲 山田哲也 西真貴子 升田紫 久保田みどり 志鎌明人 宝田亜矢子 高梨幹生 高瀬暁 岡崎佐智子 飯塚陽子 岡崎啓明 塩田清二 位高啓史 片岡一則 新島旭 片桐秀樹 山田信博 島野仁 門脇孝
  • Organizer: 第57回日本糖尿病学会
  • Place of Presentation: 大阪
  • Year and Date: 2014-05-22 – 2014-05-24
  • Invited
• [Presentation] グリコーゲン減少を神経が感知して脂肪酸エネルギー利用を促す (2014)
  • Author(s): 泉田欣彦
  • Organizer: 日本臨床分子医学会
  • Place of Presentation: 東京 (東京国際フォーラム）
• [Presentation] グリコーゲン減少を神経が感知して脂肪酸エネルギー利用を促す (2013)
  • Author(s): 泉田欣彦
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 熊本
• [Presentation] グリコーゲン減少を神経が感知して脂肪酸エネルギー利用を促す (2013)
  • Author(s): 泉田欣彦
  • Organizer: 日本動脈硬化学会
  • Place of Presentation: 東京 （京王プラザホテル）
• [Presentation] グリコーゲン減少を神経が感知して脂肪酸エネルギー利用を促す (2013)
  • Author(s): 泉田欣彦
  • Organizer: 日本肥満学会
  • Place of Presentation: 東京 （東京国際フォーラム）
• [Book] 最新醫學 (2015)
  • Author(s): 泉田欣彦
  • Total Pages: 4
  • Publisher: 最新医学社
• [Book] BIO Clinica (2015)
  • Author(s): 泉田欣彦
  • Total Pages: 4
  • Publisher: 北隆館/ニューサイエンス社
• [Book] 糖尿病学2014 (2014)
  • Author(s): 泉田欣彦
  • Total Pages: 135
  • Publisher: 診断と治療社
• [Book] 糖尿病２０1４ (2014)
  • Author(s): 泉田欣彦 など
  • Publisher: 診断と治療社