Neural mechanism regulating body weight and glucose metabolism via orexin receptors

• Project/Area Number: 25460318
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Environmental physiology(including physical medicine and nutritional physiology)
• Research Institution: Toho University
• Principal Investigator: FUNATO Hiromasa 東邦大学, 医学部, 准教授 (90363118)
• Co-Investigator(Kenkyū-buntansha): TAKASE Kenkichi 自治医科大学, 医学部, 教授 (80381474)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 体重制御 / 神経ペプチド / 糖代謝 / 機能神経解剖学 / 肥満 / 摂食

Outline of Final Research Achievements

We examined the body weight regulation via hypothalamic neuropeptides. We showed the differential roles of orexin receptors in energy metabolism. Orexin receptor signalings enhance mTORC1 singaling. Orexin-overexpression mice fed with a high-fat diet showed stronger mTORC1 signaling in their brains.　Meta-analysis revealed that MCH-signaling-deficient mice suppress body weight gain due to increased energy expenditure.

Research Products

• [Journal Article] High-fat diet feeding alters olfactory-, social-, and reward-related behaviors of mice independent of obesity. (2016)
  • Author(s): Takase K, Tsuneoka Y, Oda S, Kuroda M, Funato H
  • Journal Title: Obesity Volume: 4 Issue: 4 Pages: 886-894
  • DOI: 10.1002/oby.21441
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sleep as a biological problem: an overview of frontiers in sleep research (2016)
  • Author(s): Kanda T, Tsujino N, Kuramoto E, Koyama Y, Susaki EA, Chikahisa S, Funato H
  • Journal Title: J Physiol Sci Volume: 66 Issue: 1 Pages: 1-13
  • DOI: 10.1007/s12576-015-0414-3
  • Peer Reviewed / Open Access
• [Journal Article] 眠気の正体を求めて ―フォワード・ジェネティクスによる睡眠覚醒制御機構の解明― (2015)
  • Author(s): 船戸弘正
  • Journal Title: 実験医学 Volume: 33 Pages: 2057-2062
• [Journal Article] Orexin/Hypocretin Activates mTOR Complex 1 (mTORC1) via an Erk/Akt-independent and Calcium-stimulated Lysosome v-ATPase Pathway (2014)
  • Author(s): Zhiqiang Wang, Shimeng Liu, Miyo Kakizaki, Yuuki Hirose, Yukiko Ishikawa, Hiromasa Funato, Masashi Yanagisawa, Yonghao Yu，Qinghua Liu
  • Journal Title: Journal of Biological Chemistry Volume: 289 Issue: 46 Pages: 31950-31959
  • DOI: 10.1074/jbc.m114.600015
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Meta-analysis of melanin-concentrating hormone signaling-deficient mice on behavioral and metabolic phenotypes (2014)
  • Author(s): Kenkichi Takase, Kenichi Kikuchi, Yousuke Tsuneoka, Satoko Oda, Masaru Kuroda, Hiromasa Funato
  • Journal Title: PLoS One Volume: 9 Issue: 6 Pages: e99961-e99961
  • DOI: 10.1371/journal.pone.0099961
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A subset of thalamocortical projections to the retrosplenial cortex possesses two vesicular glutamate transporter isoforms, VGluT1 and VGluT2, in axon terminals as well as somata. (2014)
  • Author(s): Satoko Oda, Hiromasa Funato, Fumi Sato, Satomi Adachi-Akahane, Masanori Ito, Kenkichi Takase, Masaru Kuroda
  • Journal Title: Journal of Comparative Neurology Volume: 522 Issue: 9 Pages: 2089-2106
  • DOI: 10.1002/cne.23519
  • Peer Reviewed
• [Journal Article] Monoaminergic and neuropeptidergic neurons have distinct expression profiles of histone deacetylases (2013)
  • Author(s): Kenkichi Takase, Satoko Oda, Masaru Kuroda, Hiromasa Funato
  • Journal Title: PLoS One Volume: 8 Issue: 3 Pages: e58473-e58473
  • DOI: 10.1371/journal.pone.0058473
  • Peer Reviewed
• [Presentation] Identification of Mc4r mutation through obesity screening of ENU-mutagenized mice (2016)
  • Author(s): Mohammad Sarowar Hossain, Fuyuki Asano, Tomoyuki Fujiyama, Chika Miyoshi, Makito Sato, Aya Ikkyu, Satomi Kanno, Noriko Hotta, Miyo Kakizaki, Ikuo Miura, Hideki Kaneda, Tomohiro Suzuki, Shigeharu Wakana, Hiromasa Funato, Masashi Yanagisawa
  • Organizer: 第121回日本解剖学会学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-29
• [Presentation] ランダム点突然変異マウスの肥満スクリーニングによるSim1遺伝子変異の同定 (2016)
  • Author(s): 浅野冬樹 Mohammad Sarowar Hossain 藤山知之 三好千香 佐藤牧人 一久綾 管野里美 堀田範子 柿崎美代 三浦郁生 金田秀貴 鈴木智広 若菜茂晴 船戸弘正 柳沢正史
  • Organizer: 第121回日本解剖学会学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-29
• [Presentation] 前頭前皮質におけるムスカリン受容体Ｍ1の興奮性および抑制性細胞における局在分布の比較 (2016)
  • Author(s): 小田哲子、船戸弘正、恒岡洋右、吉田さちね、黒田 優
  • Organizer: 第121回日本解剖学会学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-29
• [Presentation] 生得的社会行動を制御する内側視索前野の機能解剖学的解析 (2016)
  • Author(s): 恒岡洋右, 吉田さちね, 小田哲子, 黒田優, 船戸弘正
  • Organizer: 第121回日本解剖学会学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] High-fat diet feeding alters social behaviors and sensorimotor system of mice independent of obesity (2015)
  • Author(s): Hiromasa Funato, Kenkichi Takase, Satoko Oda, Yousuke Tsuneoka, Masaru Kuroda
  • Organizer: Keystone Symposia Conference "Diabetes: New Insights into Molecular Mechanisms and Therapeutic Strategies"
  • Place of Presentation: ウェスティン都ホテル（京都府京都市）
  • Year and Date: 2015-10-26
  • Int'l Joint Research
• [Presentation] オレキシンによる体重制御機構 (2015)
  • Author(s): 船戸弘正
  • Organizer: 第22回 日本行動神経内分泌研究会
  • Place of Presentation: 神戸大学（兵庫県神戸市）
  • Year and Date: 2015-03-24
  • Invited
• [Presentation] Newly-identified sexually dimorphic gene expressions in the mouse medial preoptic area of hypothalamus. (2015)
  • Author(s): Yousuke Tsuneoka, Kenkichi Takase, Satoko Oda, Masaru Kuroda, Hiromasa Funato
  • Organizer: 第119回日本解剖学会・第92回生理学会合同大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-03-23
• [Presentation] Forward genetic approach to identify novel genes regulating sleep/wakefulness behavior (2015)
  • Author(s): Hiromasa Funato
  • Organizer: 第119回日本解剖学会・第92回生理学会合同大会
  • Place of Presentation: 神戸国際会議場（兵庫県神戸市）
  • Year and Date: 2015-03-23
• [Presentation] Identification of a single nucleotide substitution specific to the Sleepy mutant mouse pedigree by linkage analysis and whole exome sequencing (2014)
  • Author(s): Hiromasa Funato, Chika Miyoshi, Makito Sato, Aya Ikkyu, Noriko Hotta, Miyo Kakizaki, Satomi Kanno, Kanako Harano, Fuyuki Asano, Tomoyuki Fujiyama, Tomohiro Suzuki, Shigeraru Wakana, Masashi Yanagisawa
  • Organizer: Neuroscience 2014
  • Place of Presentation: 米国Washington DC
  • Year and Date: 2014-11-17
• [Presentation] Identification of a single nucleotide substitution specific to the Sleepy mutant mouse pedigree by linkage analysis and whole exome sequencing (2014)
  • Author(s): 船戸弘正 三好千香 佐藤牧人 一久綾 堀田範子 柿崎美代 管野里美 原野加奈子 浅野冬樹 藤山知之 鈴木智広 若菜茂晴 柳沢正史
  • Organizer: 第37回日本神経科学学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-09-12
• [Presentation] A subset of thalamocortical projections to the retrosplenial cortex possesses both VGluT1 and VGluT2
  • Author(s): Satoko Oda, Hiromasa Funato, Fumi Sato, Satomi Adachi-Akahane, Masanori Ito, Kenkichi Takase, Masaru Kuroda
  • Organizer: 第119回日本解剖学会学術集会
  • Place of Presentation: 自治医科大学（栃木県下野市）
• [Presentation] 摂食関連神経ペプチド産生細胞ネットワークにおけるヒストン脱アセチル化酵素の発現
  • Author(s): 恒岡洋右 高瀬堅吉 黒田優 船戸弘正
  • Organizer: 第119回日本解剖学会学術集会
  • Place of Presentation: 自治医科大学（栃木県下野市）
• [Presentation] Forward genetic analysis of ENU mutagenized mice identified multiple pedigrees exhibiting heritable sleep/wake abnormalities.
  • Author(s): Hiromasa Funato, Chika Miyoshi, Makito Sato, Aya Ikkyu, Mariko Isshiki, Yuto Goto, Kanako Harano, Satomi Kanno, Miyo Kakizaki, Sayuki Kiatagawa, Sachiko Tomita, Tomohiro Suzuki, Shigeharu Wakana, Masashi Yanagisawa
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館（京都府京都市）
• [Presentation] Statistical inference of neural circuits responsible for behavioral parameters of mice
  • Author(s): Kenkichi Takase, Kenichi Kikuchi, Satoko Oda, Masaru Kuroda, Hiromasa Funato
  • Organizer: Neuro2013
  • Place of Presentation: 国立京都国際会館（京都府京都市）