Hepato-Vagal Nerve Pathway Switches Energy Source from Carbohydrate to Fat during Fasting

• Project/Area Number: 22790850
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• 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)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: メタボリックシンドローム / 神経 / エネルギー・糖脂質代謝異常 / ニューロ・バイオインフォマティクス / センシング・デバイス・システム

Research Abstract

During fasting, mammals maintain energy balance by shifting from carbohydrate fuel to fat burning.
The liver mobilizes glucose from its glycogen stores in the early stages of fasting. As fasting progresses and glycogen reserves are depleted, the adipose tissue provides substrates for energy metabolism. This synchronization of hepatic carbohydrate and adipose lipid metabolism is critical for the normal fasting response. Here, we show that depletion of liver glycogen triggers to switching the energy sources from hepatic carbohydrate to adipose lipid during fasting via hepatic neuronal pathway and causes corresponding increases in fatty acid oxidation ; Interrupting nerve signals from liver in fasting rodents and the preceding overload of glycogen in liver by the overexpression of both GYS2(glycogen synthase 2), TFE3 or siPYGL(shRNA targeting for phosphorylase glycogen liver) adenovirus fail to fully induce adipose lipolysis after a prolonged fast. Conversely, siGYS2 adenovirus-mediated glycogen depletion in liver promotes lipolysis in adipose tissue via PKA(cAMP-dependent protein kinase)-HSL(hormone-sensitive lipase) dependent pathway. These results reveal a hepatic glycogen breakdown trigger a Liver. Brain. Adipose neural axis to regulate a mobilizing adipose lipid fuel and demonstrate an important role for hepatic neuronal signal in coordinately regulating carbohydrate and fatty acid metabolism during the progression from fasting to starvation.

Research Products

• [Journal Article] Abrogation of neutral cholesterol ester hydrolytic activity causes adrenal enlargement (2011)
  • Author(s): Ohta K、Izumida Y et al
  • Journal Title: Biochem Biophys Res Commun Volume: 7 ; 404(1) Pages: 254-60
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/21111707
  • Peer Reviewed
• [Journal Article] Abrogation of neutral cholesterol ester hydrolytic activity causes adrenal enlargement (2011)
  • Author(s): Ohta K, et al.
  • Journal Title: Biochem Biophys Res Commun Volume: 7;404(1) Pages: 254-60
  • Peer Reviewed
• [Journal Article] Polyunsaturated fatty acids selectively suppress sterol regulatory element-binding protein-1 through proteolytic processing and autoloop regulatory circuit (2010)
  • Author(s): Takeuchi Y, Yahagi N, Izumida Y et al
  • Journal Title: J Biol Chem Volume: 9 ; 285(15) Pages: 11681-91
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/20145241
  • Peer Reviewed
• [Journal Article] Polyunsaturated fatty acids selectively suppress sterol regulatory element-binding protein-1 through proteolytic processing and autoloop regulatory circuit. (2010)
  • Author(s): Takeuchi Y, Yahagi N, Izumida Y, et al.
  • Journal Title: J Biol Chem Volume: 9;285(15) Pages: 11681-91
  • Peer Reviewed
• [Presentation] 飢餓における自律神経を介した肝・脂肪代謝制御の解明-Hepato_vagal nerve pathway modulates carbohydrate-lipid balancing- (2012)
  • 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、高梨幹生、高瀬暁、飯塚陽子、影山晴秋、塩田清二、位高啓史、片岡一則、新島旭、片桐秀樹、岡芳知、山田信博、野仁、門脇孝
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 横浜日本
  • Year and Date: 2012-05-19
• [Presentation] 飢餓における自律神経を介した肝・脂肪代謝制御の解明-Hepato_vagal nerve pathway modulates carbohydrate-lipid balancing- (2011)
  • 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、高梨幹生、高瀬暁、飯塚陽子、影山晴秋、塩田清二、位高啓史、片岡一則、新島旭、片桐秀樹、岡芳知、山田信博、島野仁、門脇孝
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 札幌日本
  • Year and Date: 2011-05-19
• [Presentation] 飢餓における自律神経を介した肝・脂肪代謝制御の解明-Hepato_vagal nerve pathway modulates carbohydrate-lipid balancing- (2011)
  • Author(s): 泉田欣彦, 他
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 札幌
  • Year and Date: 2011-05-19
• [Presentation] Kadowaki TakashiHepato-Vagal Nerve Pathway Switches Energy Source from Carbohydrate to Fat during Fasting (2011)
  • Author(s): Izumida Yoshihiko, Yahagi Naoya, Takeuchi Yoshinori, Nishi Makiko, Yamada Tetsuya, Kubota Midori, Kumagai Masayoshi, Ota Keisuke, Takase Satoru, Igarashi Masaki, Sekiya Motohiro, Izuka Yoko, Kageyama Haruaki, Shiota Seiji, Itaka Keiji, Kataoka Kazunori, Niijima Akira, Katagiri Hideki, Oka Yoshitomo, Osuga Jun-ichi, Yamada Nobuhiro, Shimano Hitoshi, Ohashi Ken
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜日本
• [Presentation] Hepato-Vagal Nerve Pathway Switches Energy Source from Carbohydrate to Fatduring Fasting (2011)
  • Author(s): Yoshihiko Izumida, et al.
  • Organizer: 日本分子生物学会
  • Place of Presentation: 横浜
• [Presentation] Hepato-Vagal Nerve Pathway Switches Energy Source from Carbohydrate to Fat during Fasting (2010)
  • Author(s): Izumida Yoshihiko, Yahagi Naoya, Takeuchi Yoshinori, Nishi Makiko, Yamada Tetsuya, Kubota Midori, Kumagai Masayoshi, Ota Keisuke, Takase Satoru, Igarashi Masaki, Sekiya Motohiro, Izuka Yoko, Kageyama Haruaki, Shiota Seiji, Itaka Keiji, Kataoka Kazunori, Niijima Akira, Katagiri Hideki, Oka Yoshitomo, Osuga Jun-ichi, Yamada Nobuhiro, Shimano Hitoshi, Ohashi Ken, Kadowaki Takashi
  • Organizer: The 2010 IDF WPR Conference
  • Place of Presentation: Busan, Korea
  • Year and Date: 2010-10-19
• [Presentation] Hepato-Vagal Nerve Pathway Switches Energy Source from Carbohydrate to Fat during Fasting (2010)
  • Author(s): Izumida Yoshihiko, Yahagi Naoya, Takeuchi Yoshinori, Nishi Makiko, Yamada Tetsuya, Kubota Midori, Kumagai Masayoshi, Ota Keisuke, Takase Satoru, Igarashi Masaki, Sekiya Motohiro, Izuka Yoko, Kageyama Haruaki, Shiota Seiji, Itaka Keiji, Kataoka Kazunori, Niijima Akira, Katagiri Hideki, Oka Yoshitomo, Osuga Jun-ichi, Yamada Nobuhiro, Shimano Hitoshi, Ohashi Ken, Kadowaki Takashi
  • Organizer: 日本動脈硬化学会
  • Place of Presentation: 岐阜,日本
  • Year and Date: 2010-07-15
• [Presentation] 飢餓における自律神経を介した肝・脂肪代謝制御の解明-Hepatic neuronal pathway switches mobilizing energy sources from carbohydrates to lipids during fasting- (2010)
  • 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、高梨幹生、高瀬暁、飯塚陽子、影山晴秋、塩田清二、位高啓史、片岡一則、新島旭、片桐秀樹、岡芳知、山田信博、島野仁、門脇孝
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 岡山,日本
• [Presentation] Hepato-Vagal Nerve Pathway Switches Energy Source from Carbohydrate to Fat during Fasting (2010)
  • Author(s): Izumida Yoshihiko, Yahagi Naoya, Takeuchi Yoshinori, Nishi Makiko, Yamada Tetsuya, Kubota Midori, Kumagai Masayoshi, Ota Keisuke, Takase Satoru, Igarashi Masaki, Sekiya Motohiro, Izuka Yoko, Kageyama Haruaki, Shiota Seiji, Itaka Keiji, Kataoka Kazunori, Niijima Akira, Katagiri Hideki, Oka Yoshitomo, Osuga Jun-ichi, Yamada Nobuhiro, Shimano Hitoshi, Ohashi Ken, Kadowaki Takashi
  • Organizer: 日本分子生物学会
  • Place of Presentation: 神戸,日本
• [Presentation] Hepato-Vagal Nerve Pathway Switches Energy Source from Carbohydrate to Fat during Fasting (2010)
  • Author(s): Izumida Yoshihiko, Yahagi Naoya, Takeuchi Yoshinori, Nishi Makiko, Yamada Tetsuya, Kubota Midori, Kumagai Masayoshi, Ota Keisuke, Takase Satoru, Igarashi Masaki, Sekiya Motohiro, Izuka Yoko, Kageyama Haruaki, Shiota Seiji, Itaka Keiji, Kataoka Kazunori, Niijima Akira, Katagiri Hideki, Oka Yoshitomo, Osuga Jun-ichi, Yamada Nobuhiro, Shimano Hitoshi, Ohashi Ken, Kadowaki Takashi
  • Organizer: American Diabetes Association
  • Place of Presentation: Orlando, Florida, USA
• [Presentation] 飢餓における自律神経を介した肝・脂肪代謝制御の解明-Hepatic neuronal pathway switches mobilizing energy sources from car bohydrates to lipids during fasting- (2010)
  • Author(s): 泉田欣彦, ほか
  • Organizer: 日本糖尿病学会
  • Place of Presentation: 岡山,日本
• [Remarks]
  • URL: http://www.h.u-tokyo.ac.jp/patient/depts/md_md/index.html