Discovery of a novel inter-organ metabolic communication system

• Project/Area Number: 23390238
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Tohoku University
• Principal Investigator: KATAGIRI Hideki 東北大学, 大学院・医学系研究科, 教授 (00344664)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000); Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000); Fiscal Year 2011: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
• Keywords: 糖尿病 / 肥満 / 脳・神経 / 脂質代謝

Research Abstract

We have found that adaptive thermogenesis induced by brown adipose tissue (BAT) was markedly suppressed, when hepatic glucose metabolism was enhanced by glucokinase overexpression. This liver-to-BAT communication is mediated by a neuronal relay consisting of afferent vagal and efferent sympathetic nerves. This inter-tissue system seems to function as a feed-forward mechanism favoring energy storage. This mechanism might have worked advantageously under conditions of repetitive excesses and shortagesof food. Unfortunately, however, in the current age of constant plenty, this system seems to trigger obesity development. In fact, we further found that this system contributes to determining obesity predisposition among murine strains.

Research Products

• [Journal Article] Chronic mild stress alters circadian expressions ofmolecular clock genes in the liver (2012)
  • Author(s): Takahashi K, Yamada T, Tsukita S, Kaneko K, Shirai Y, Munakata Y, Ishigaki Y, Imai J, Uno K, Hasegawa Y, Sawada S, Oka Y, Katagiri H.
  • Journal Title: Am J Physiol Endocrinol Metab Volume: 304(3) Issue: 3 Pages: E301-E309
  • DOI: 10.1152/ajpendo.00388.2012
  • Peer Reviewed
• [Journal Article] Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals (2012)
  • Author(s): Tsukita S, Yamada T, Uno K, Takahashi K, Kaneko K, Ishigaki Y, Imai J, Hasegawa Y, Sawada S, Ishihara H, Oka Y, Katagiri H.
  • Journal Title: Cell Metab Volume: 16(6) Issue: 6 Pages: 825-832
  • DOI: 10.1016/j.cmet.2012.11.006
  • Peer Reviewed
• [Journal Article] Importance of endothelial NF-κB signaling in vascular remodeling and aortic aneurysm formation (2012)
  • Author(s): Saito T, Hasegawa Y, Ishigaki Y, Yamada T, Gao J, Imai J, Uno K, Kaneko K, Ogihara T, Shimosawa T, Asano T, Fujita T, Oka Y, Katagiri H.
  • Journal Title: Cardiovascular Research Volume: 97(1) Issue: 1 Pages: 106-114
  • DOI: 10.1093/cvr/cvs298
  • Peer Reviewed
• [Journal Article] A case of slowly progressive type 1 diabetes maintaining insulin independence for 10 years with α-glucosidase inhibitor monotherapy (2012)
  • Author(s): Munakata Y, Yamada T, Takahashi K, Tsukita S, Takahashi K, Sawada S, Imai J, Ishigaki Y, Oka Y, Katagiri H.
  • Journal Title: Internal Medicine Volume: 51(24) Pages: 3391-3394
  • Peer Reviewed
• [Journal Article] Brain-derived neurotrophic factor protects against cardiac dysfunction after myocardial infarction via a central nervous system-medeiated pathway (2012)
  • Author(s): Okada S, Yokoyama M, Toko H, Tateno K, Moriya J, Shimizu I, Nojima A, Ito T, Yoshida Y, Kobayashi Y, Katagiri H, Minamino T, Komuro I
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32(8) Issue: 8 Pages: 1902-9
  • DOI: 10.1161/atvbaha.112.248930
  • Peer Reviewed
• [Journal Article] Atf6α-null mice are glucose intolerant due to pancreatic β-cell failure on a high-fat diet but partially resistant to diet-induced insulin resistance (2012)
  • Author(s): M.Usui, S.Yamaguchi, Y.Tanji, R.Tominaga, Y.Ishigaki, M.Fukumoto, H.Katagiri, K.Mori, Y.Oka, H.Ishihara
  • Journal Title: Metabol Volume: (in press) Issue: 8 Pages: 1118-28
  • DOI: 10.1016/j.metabol.2012.01.004
  • Peer Reviewed
• [Journal Article] Blockade of the nuclear factor-κB pathway in the endothelium prevents insulin resistance and prolongs life spans (2012)
  • Author(s): Hasegawa Y, Fujita T, et al.
  • Journal Title: Circulation Volume: 125 Issue: 9 Pages: 1122-1133
  • DOI: 10.1161/circulationaha.111.054346
  • Peer Reviewed
• [Journal Article] Hepatic peroxisome proliferator-activated receptor-{gamma}-fat-specific protein 27 pathway contributes to obesity-related hypertension via afferent vasal signals (2012)
  • Author(s): Uno K, Yamada T, Ishigaki Y, Imai J, Hasegawa Y, Gao J, Kaneko K, Matsusue K, Yamazaki T, Oka Y, Katagiri H
  • Journal Title: Eur Heart J Volume: (In Press) Issue: 10 Pages: 1279-1289
  • DOI: 10.1093/eurheartj/ehr265
  • Peer Reviewed
• [Journal Article] A case of slowly progressive type 1 diabetes maintaining insulin independence for 10 years with α-glucosidase inhibitor monotherapy. (2012)
  • Author(s): Munakata Y, Yamada T, Takahashi K, Tsukita S, Takahashi K, Sawada S, Imai J, Ishigaki Y, Oka Y, Katagiri H.
  • Journal Title: Internal Medicine Volume: 51(24) Pages: 3391-3394
  • Peer Reviewed
• [Journal Article] Recurrent hypoglycemia during pregnancies in a woman with multiple autoantibodies including anti-insulin receptor antibody and anti-platelet antibody, whose serum lowered murine blood glucose levels and phosphorylated insulin receptor of CHO-IR cells (2011)
  • Author(s): Toshihiro M, Katagiri H, Kataoka K, Fukushima A, Segawa T, Fujiwara T, Hikichi I, Takebe N, Satoh J
  • Journal Title: Endocr J Volume: 58(12) Pages: 1037-1043
  • NAID: 10030392465
  • Peer Reviewed
• [Journal Article] Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle (2011)
  • Author(s): Sugita S, Kamei Y, Akaike F, Suganami T, Kanai S, Hattori M, Manabe Y, Fujii N, Takai-Igarashi T, Tadaishi M, Oka J, Aburatani H, Yamada T, Katagiri H, Kakehi S, Tamura Y, Kubo H, Nishida K, Miura S, Ezaki O, Ogawa Y
  • Journal Title: PLoS One Volume: 6(5) Issue: 5 Pages: e20467-e20467
  • DOI: 10.1371/journal.pone.0020467
  • Peer Reviewed
• [Journal Article] Involvement of endoplasmic stress protein C/EBP homologous protein in arteriosclerosis acceleration with augmented biological stress responses (2011)
  • Author(s): Gao J, Ishigaki Y, Yamada T, Kondo K, Yamaguchi S, Imai J, Uno K, HasegawaY, Sawada S, Ishihara H, Oyadomari S, Mori M, Oka Y, Katagiri H
  • Journal Title: Circulation Volume: 124 Issue: 7 Pages: 830-839
  • DOI: 10.1161/circulationaha.110.014050
  • Peer Reviewed
• [Journal Article] 4F2hc stabilizes GLUT1 protein and increases glucose transport activity (2011)
  • Author(s): Ohno H, Nakatsu Y, Sakoda H, Kushiyama A, Ono H, Fujishiro M, Otani Y, Okubo H, Yoneda M, Fukushima T, Kamata H, Nishimura F, Kurihara H, Katagiri H, Oka Y, Asano T
  • Journal Title: Am J Physiol Cell Physiol Volume: 300(5) Issue: 5 Pages: 1047-54
  • DOI: 10.1152/ajpcell.00416.2010
  • Peer Reviewed
• [Journal Article] Frequent loss of genome gap region in 4p16.3 subtelomere in early-onset type 2 diabetes mellitus (2011)
  • Author(s): Kudo H, Emi M, Ishigaki Y, Tsunoda U, Hinokio Y, Ishii M, Sato H, Yamada T, Katagiri H, Oka Y
  • Journal Title: Exp Diabetes Res Volume: 2011 Pages: 498460-498460
  • DOI: 10.1155/2011/498460
  • Peer Reviewed
• [Journal Article] Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with IRS-1 and enhances insulin actions and adipogenesis (2011)
  • Author(s): Nakatsu Y, Sakoda H, Kushiyama A, Zhang J, Ono H, Fujishiro M, Kikuchi T, Fukushima T, Yoneda M, Ohno H, Horike N, Kanna M, Tsuchiya Y, Kamata H, Nishimura F, Isobe T, Ogihara T, Katagiri H, Oka Y, Takahashi SI, Kurihara H, Uchida T, Asano T
  • Journal Title: J Biol Chem Volume: 286 Issue: 23 Pages: 20812-20822
  • DOI: 10.1074/jbc.m110.206904
  • Peer Reviewed
• [Presentation] Neuronal Information Highways for Systemic Regulation of Glucose and Energy Metabolism (2013)
  • Author(s): Katagiri H.
  • Organizer: International Symposium on Development of Medical Technologies for Treating Intractable Cancers andCardiovascular Diseases
  • Place of Presentation: Tokyo,Japan
• [Presentation] Neuronal Information Highways for Systemic Regulation of Glucose and Energy Metabolism (2013)
  • Author(s): Hideki Katagiri
  • Organizer: International Symposium on Development of Medical Technologies for Treating Intractable Cancers and Cardiovascular Diseases
  • Place of Presentation: Tokyo
  • Invited
• [Presentation] Regulation ofpancreatic beta-cells by Inter-organ Networks (2012)
  • Author(s): Imai J, Katagiri H.
  • Organizer: 第4回アジア糖尿病学会・第9回国際糖尿病連合西太平洋総会
  • Place of Presentation: Kyoto,Japan
  • Year and Date: 2012-11-27
• [Presentation] Metabolic Information Highway～個体レベルでの代謝制御機構～ (2012)
  • Author(s): 片桐秀樹
  • Organizer: 神経組織の成長・再生・移植研究会第27回学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-10-27
• [Presentation] 糖代謝と自律神経:神経ネHighway～個体レベルでの代謝制御機構～ (2012)
  • Author(s): 片桐秀樹
  • Organizer: 神経組織の成長・再生・移植研究会第27回学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-10-27
• [Presentation] 個体レベルでの代謝調節と循環～血圧から寿命の制御まで～ (2012)
  • Author(s): 片桐秀樹
  • Organizer: 第1回日本肺循環学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2012-09-22
• [Presentation] 非侵襲的陽圧換気療法の使用により著名な体重減少を呈した肥満低換気症候群の一例 (2012)
  • Author(s): 浅井洋一郎,宇野健司,田中満実子,宗像佑一郎,高橋圭,今井淳太,山田哲也,石垣泰,岡芳知,片桐秀樹
  • Organizer: 第30回肥満治療学会学術総会
  • Place of Presentation: 東京
  • Year and Date: 2012-06-29
• [Presentation] 神経系を介した臓器間相互作用による体重調節機構 (2012)
  • Author(s): 山田哲也,片桐秀樹,岡芳知
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-04-21
• [Presentation] 臓器間ネットワークによる膵β細胞制御機構 (2012)
  • Author(s): 今井淳太,片桐秀樹
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-04-19
• [Presentation] 糖尿病と栄養-東日本大震災を乗り越えて- (2012)
  • Author(s): 片桐秀樹
  • Organizer: 第19回日本健康体力栄養学会
  • Place of Presentation: 神戸
  • Year and Date: 2012-03-10
• [Presentation] 神経系を介した臓器間相互作用による体重調節 (2012)
  • Author(s): 山田哲也,岡芳知,片桐秀樹
  • Organizer: 第16回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京
• [Presentation] 多臓器連環による循環・代謝のダイナミズム (2012)
  • Author(s): 片桐秀樹
  • Organizer: 第16回日本心血管内分泌代謝学会総会
  • Place of Presentation: 東京
• [Presentation] Bach 1 dificiency protects pancreatic bepa cells from oxidative stress injury (2012)
  • Author(s): Kondo K, Ishigaki Y, Gao J, Yamada T, Imai J, Sawada S, Muto A, Oka Y,Igarashi K, Katagiri H.
  • Organizer: 48th European Association for the Study of Diabetes Annual Meeting
  • Place of Presentation: Berlin,Germany
• [Presentation] 動脈硬化を操る代謝シグナルネットワークの解明から治療へThe atherosclerosis puzzle:Bringing up new Matabolic pieces (2012)
  • Author(s): 片桐秀樹
  • Organizer: 第44回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 福岡
• [Presentation] Hepatic Glucokinase Negatively Regulates BAT Thermogenesis via a Neural Pathway (2012)
  • Author(s): Tsukita S, Yamada T, Uno K, Oka Y, Katagiri H.
  • Organizer: 72nd American Diabetes Association
  • Place of Presentation: Philadelphia,USA
• [Presentation] mTOR抑制因子であるDEPTORが糖エネルギー代謝に与える影響の解明 (2012)
  • Author(s): 千葉弓子,宇野健司,片桐秀樹
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] 継続した避難所巡回診療により見えてきた災害時の糖尿病医療の問題点とその対策 (2012)
  • Author(s): 児玉慎二郎,石垣泰,今井淳太,山田哲也,岡芳知,片桐秀樹
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] 褐色脂肪組織における熱産生調節につながる組織間ネットワーク (2012)
  • Author(s): 突田壮平,山田哲也,宇野健司,高橋圭,浅井洋一郎,白井勇太,宗像佑一郎,金子慶三,澤田正二郎,長谷川豊,今井淳太,石垣泰,岡芳知,片桐秀樹
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
• [Presentation] 臓器間ネットワークとメタボリックシンドローム (2012)
  • Author(s): 片桐秀樹
  • Organizer: 第49回日本臨床分子医学会学術集会
  • Place of Presentation: 京都
• [Presentation] 全身における代謝調節と臓器間神経ネットワーク (2012)
  • Author(s): 片桐秀樹
  • Organizer: 第46回糖尿病学の進歩
  • Place of Presentation: 盛岡
• [Presentation] 糖代謝と自律神経：神経ネットワークの解明 (2012)
  • Author(s): 片桐 秀樹
  • Organizer: 第55回日本糖尿病学会年次学術集会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 動脈硬化を操る代謝シグナルネットワークの解明から治療へ The atherosclerosis puzzle:Bringing up new Matabolic pieces (2012)
  • Author(s): 片桐 秀樹
  • Organizer: 第44回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 福岡
  • Invited
• [Presentation] 多臓器連関による循環・代謝のダイナミズム (2012)
  • Author(s): 片桐 秀樹
  • Organizer: 第16回日本心血管内分泌代謝学会総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 神経系を介した臓器間相互作用による体重調整 (2012)
  • Author(s): 山田哲也、岡芳知、片桐秀樹
  • Organizer: 第16回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Bach1 deficiency protects pancreatic beta cells from oxidative stress injury (2012)
  • Author(s): Keiichi Kondo, Y. Ishigaki, J. Gao, T. Yamada, J. Imai, S. Sawada, A. Muto, Y. Oka, K. Igarashi, H. Katagiri
  • Organizer: 48th European Association for the Study of Diabetes Annual Meeting
  • Place of Presentation: Berlin,Germany
  • Invited
• [Presentation] 多臓器円環のダイナミクス研究に関する学術的意義と推進上の課題 (2011)
  • Author(s): 片桐秀樹
  • Organizer: 学術シンポジウム「多臓器円環のダイナミクス」
  • Place of Presentation: 東京
  • Year and Date: 2011-10-08
• [Presentation] 脳神経科学と内科疾患との融合研究事例 (2011)
  • Author(s): 片桐秀樹
  • Organizer: 科学技術振興機構研究開発戦略センター戦略イニシアティブ「ホメオダイナミクス」フォローアップワークショップ
  • Place of Presentation: 東京
  • Year and Date: 2011-06-18
• [Presentation] Japan Statement for Metabolic surgery代謝内科からみたmetabolic surgeryの有用性 (2011)
  • Author(s): 石垣泰, 片桐秀樹
  • Organizer: 第29回日本肥満症治療学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-10
• [Presentation] Regulation of insulin secretion by inter-organ networks (2011)
  • Author(s): Imai J, Katagiri H.
  • Organizer: Workshop"Programming Beta Cell Development, Impairment and regeneration"
  • Place of Presentation: Helsinger,Denmark
• [Presentation] 臓器間神経ネットワークによる全身での代謝調節 (2011)
  • Author(s): 片桐秀樹
  • Organizer: 第32回日本肥満学会
  • Place of Presentation: 淡路
• [Presentation] Neuronal Information Highways for Maintaining Glucose and Energy Homeostasis (2011)
  • Author(s): Katagiri H.
  • Organizer: The 34th Annual Meeting of the Japan -Neuroscience Society-Neuroscience Mind-
  • Place of Presentation: Yokohama,Japan
• [Presentation] Metabolic Information Highways～神経ネットワークによる個体レベルでの代謝調節機構～ (2011)
  • Author(s): 片桐秀樹
  • Organizer: 第29回内分泌代謝学サマーセミナー
  • Place of Presentation: 仙台
• [Presentation] 災害時の糖尿病医療大学病院/地域の中核病院の役割は (2011)
  • Author(s): 石垣泰, 片桐秀樹
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] 災害時の対策市民公開講座変わる!「糖尿病」新しい時代の、新しい糖尿病医療 (2011)
  • Author(s): 片桐秀樹
  • Organizer: 第54回日本糖尿病学会年次学術集会
  • Place of Presentation: 札幌
• [Presentation] 全ゲノムCNV解析による若年発症2型糖尿病患者における高頻度ゲノム欠失成人期疾患のCNV研究 (2011)
  • Author(s): 工藤宏仁, 山田哲也, 岡芳知, 片桐秀樹
  • Organizer: 遺伝医学合同学術集会2011
  • Place of Presentation: 京都
• [Presentation] Neuronal Information Highways for maintaining glucose and energy homeostasis (2011)
  • Author(s): Hideki Katagiri
  • Organizer: The 34th Annual Meeting of the Japan Neuroscience Society-Neuroscience Mind-
  • Place of Presentation: Yokohama
• [Presentation] Regulation of insulin secretion by inter-organ networks (2011)
  • Author(s): Junta Imai, Yoshitomo Oka, Hideki Katagiri
  • Organizer: Workshop "Programming Beta Cell Development, Impairment and regeneration"
  • Place of Presentation: Helsinger, Denmark
• [Presentation] 臓器間ネットワークによる膵β細胞制御機構
  • Author(s): 今井 淳太、片桐 秀樹
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] 神経系を介した臓器間相互作用による体重調節機構
  • Author(s): 山田 哲也、片桐 秀樹、岡 芳知
  • Organizer: 第85回日本内分泌学会学術総会
  • Place of Presentation: 名古屋
  • Invited
• [Presentation] 非侵襲的陽圧換気療法の使用により著明な体重減少を呈した肥満低換気症候群の一例
  • Author(s): 浅井 洋一郎、宇野 健司、田中 満実子、宗像 佑一郎、高橋 圭、今井 淳太、山田 哲也、石垣 泰、岡 芳知、片桐 秀樹
  • Organizer: 第30回日本肥満症治療学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] 個体レベルでの代謝調節と循環～血圧から寿命の制御まで～
  • Author(s): 片桐 秀樹
  • Organizer: 第1回日本肺循環学会学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Metabolic Information Highway～個体レベルでの代謝制御機構～
  • Author(s): 片桐 秀樹
  • Organizer: 神経組織の成長・再生・移植研究会第27回学術集会
  • Place of Presentation: 東京
  • Invited
• [Presentation] Regulation of pancreatic beta-cells by Inter-organ Networks
  • Author(s): Junta Imai, Hideki Katagiri
  • Organizer: 第4回アジア糖尿病学会・第9回国際糖尿病連合西太平洋総会
  • Place of Presentation: 京都
  • Invited