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Identification of novel mechanisms in obesity development.

Research Project

Project/Area Number 23591293
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionTohoku University

Principal Investigator

YAMADA Tetsuya  東北大学, 医学(系)研究科(研究院), 准教授 (90400374)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2013: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywords臓器間相互作用 / 褐色脂肪組織 / 肝臓 / 自律神経 / 迷走神経 / 交感神経 / グルコキナーゼ / 褐色脂肪 / 肥満 / 糖尿病 / エネルギー代謝
Research Abstract

Despite remarkable advancements in obesity research over the past decade, the mechanisms underlying obesity are still not fully understood. In this study, we discovered a new inter-organ neural network from the liver. In states of energy intake beyond physiological requirements, glucose metabolism changes in the liver with the induction of neuronal signal transmissions via the vagal nerve. These signals, received by the brain, result in the inactivation of sympathetic innervation of brown adipose tissue (BAT). This leads to suppression of thermogenesis in BAT and thereby favors obesity development. During periods when sufficient food was not always available, this system worked in favor of survival. However, in the current age of plenty, it is assumed to work as a mechanism flipping a metabolic switch toward obesity. Furthermore, the efficacy of the liver-to-BAT interaction differs among mouse strains and these differences may contribute to determining the obesity predispositions.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (38 results)

All 2014 2013 2012 2011 Other

All Journal Article (23 results) (of which Peer Reviewed: 23 results,  Open Access: 1 results) Presentation (15 results) (of which Invited: 7 results)

  • [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

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bach1 deficiency protects pancreatic β-cells from oxidative stress injury.2013

    • Author(s)
      Kondo K, Ishigaki Y, Gao J, Yamada T, Imai J, Sawada S, Muto A, Oka Y, Igarashi K, Katagiri H.
    • Journal Title

      Am J Physiol Endocrinol Metab.

      Volume: 305(5) Issue: 5 Pages: E641-E648

    • DOI

      10.1152/ajpendo.00120.2013

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inter-organ communications mediate crosstalk between glucose and energy metabolism. (Review)2013

    • Author(s)
      Yamada T
    • Journal Title

      Diabetol Int

      Volume: 4(3) Pages: 149-155

    • URL

      http://link.springer.com/article/10.1007%2Fs13340-013-0133-z

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a novel inter-organ mechanism favoring energy storage in over-nutrition2013

    • Author(s)
      Yamada T (corresponding author), Tsukita S, Katagiri H
    • Journal Title

      Adipocyte

      Volume: 2(4) Issue: 4 Pages: 281-284

    • DOI

      10.4161/adip.25499

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cognitive dysfunction associated with anti-glutamic acid decarboxylase autoimmunity : a case-control study2013

    • Author(s)
      Takagi M, Ishigaki Y, Uno K, Sawada S, Imai J, Kaneko K, Hasegawa Y, Yamada T, Tokita A, Iseki K, Kanno S, Nishio Y, Katagiri H, Mori E
    • Journal Title

      BMC Neurol

      Volume: 13 Issue: 1 Pages: 295-295

    • DOI

      10.1186/1471-2334-13-295

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 臓器間相互作用が司る糖代謝とエネルギー代謝のクロストーク2013

    • Author(s)
      山田哲也
    • Journal Title

      糖尿病(Journal of the Japan Diabetes Society)

      Volume: 56(10) Pages: 718-720

    • NAID

      130004905352

    • URL

      https://www.jstage.jst.go.jp/article/tonyobyo/56/10/56_718/_pdf

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cognitive dysfunction associated with anti-glutamic acid decarboxylase autoimmunity: A case-control study2013

    • Author(s)
      Takagi M, Ishigaki Y, Uno K, Sawada S, Imai J, Kaneko K, Hasegawa Y, Yamada T, Tokita A, Iseki K, Kanno S, Nishio Y, Katagiri H and Mori E
    • Journal Title

      BMC Neurol

      Volume: 13 Issue: 1 Pages: 76-76

    • DOI

      10.1186/1471-2377-13-76

    • URL

      https://pure.teikyo.jp/en/publications/27420326-bb90-462a-ab81-4bc2db7a6562

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic mild stress alters circadian expressions of molecular clock genes in the liver.2013

    • Author(s)
      Takahashi K, Yamada T (corresponding author), 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)

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Chronic mild stress alters circadian expressions of molecular clock genes in the liver2012

    • 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 Issue: 3 Pages: E301-E309

    • DOI

      10.1152/ajpendo.00388.2012

    • URL

      https://pure.teikyo.jp/en/publications/4b1787b1-1613-4809-bf93-e9df907ea8f0

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Importance of endothelial NF-κB signaling in vascular remodeling and aortic aneurysm formation2012

    • 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

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals2012

    • Author(s)
      Tsukita S, Yamada T, Uno K, Takahashi1 K, Kaneko K, Ishigaki Y, Imai J, Hasegawa Y, Sawada S, Ishihara H, Oka Y, Katagiri H
    • Journal Title

      Cell Metab

      Volume: 16(6) Pages: 825-32

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] A case of slowly progressive type 1 diabetes with insulin independence maintained for 10 years withα-glucosidase inhibitor monotherapy2012

    • Author(s)
      Munakata Y, Yamada T (corresponding author), Takahashi K, Tsukita S, Takahashi K, Sawada S, Imai J, Ishigaki Y, Oka Y, Katagiri H
    • Journal Title

      Intern Med

      Volume: 51(24) Pages: 3391-4

    • NAID

      130003308166

    • URL

      http://www.ncbi.nlm.nih.gov/pubmed/23257526

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Blockade of the nuclear factor-κB pathway in the endothelium prevents insulin resistance and prolongs life spans2012

    • Author(s)
      Hasegawa Y, Fujita T, et al.
    • Journal Title

      Circulation

      Volume: 125 Issue: 9 Pages: 1122-1133

    • DOI

      10.1161/circulationaha.111.054346

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hepatic peroxisome proliferator-activated receptor-{gamma}-fat-specific protein 27 pathway contributes to obesity-related hypertension via afferent vasal signals2012

    • 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

    • Related Report
      2013 Final Research Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] エネルギー代謝の中枢神経支配2012

    • Author(s)
      山田哲也
    • Journal Title

      糖尿病(Journal of the Japan Diabetes Society)

      Volume: 55(5) Pages: 309-312

    • NAID

      10030976789

    • URL

      http://search.jamas.or.jp/index.php

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Hepatic glucokinase modulates obesity predisposition by regulating BAT thermogenesis via neural signals2012

    • 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

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] NF-kappaB 経路と老化についての論文2012

    • Author(s)
      Hasegawa Y, Saito T, Ogihara T, Yamada T et al
    • Journal Title

      Circulation

      Volume: 125 Pages: 1122-1133

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] CHOPの動脈硬化における役割についての論文2012

    • Author(s)
      Gao J, Ishigaki Y, Yamada T, Imai J et al.
    • Journal Title

      Circulation

      Volume: 124 Pages: 830-839

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cognitive decline in a patient with anti-glutamic acid decarboxylase autoimmunity; case report2011

    • Author(s)
      Takagi M, Yamasaki H, Endo K, Yamada T, Kaneko K, Oka Y, Mori E
    • Journal Title

      BMC Neurol

      Volume: 11 Issue: 1 Pages: 156-156

    • DOI

      10.1186/1471-2377-11-156

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of endoplasmic stress protein C/EBP homologous protein in arteriosclerosis acceleration with augmented biological stress responses2011

    • 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

    • DOI

      10.1161/circulationaha.110.014050

    • URL

      https://pure.teikyo.jp/en/publications/8edda9c5-a7a4-41ee-a9c5-00e46cf10dd7

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Frequent loss of genome gap region in 4p16.3 subtelomere in early-onset type 2 diabetes mellitus2011

    • 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

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Increased systemic glucose tolerance with increased muscle glucose uptake in transgenic mice overexpressing RXRγ in skeletal muscle2011

    • 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

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Interleuki n-6 enhances glucose-stimulated insu lin secretion from pancreatic beta-cells : potential involvement of the PLC-IP3 dependent pathway.2011

    • Author(s)
      Suzuki T, Imai J, Yamada T, IshigakiY, Kaneko K, Uno K, Hasegawa Y, Ishihara H, Oka Y, Katagiri H
    • Journal Title

      Diabetes

      Volume: 60 Issue: 2 Pages: 537-547

    • DOI

      10.2337/db10-0796

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Presentation] 臓器間ネットワークからみた肥満・2型糖尿病(シンポジウム6:臓器からみた糖尿病の病態と治療)2014

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第48回糖尿病学の進歩
    • Place of Presentation
      札幌市
    • Year and Date
      2014-03-08
    • Related Report
      2013 Final Research Report
  • [Presentation] Inter-organ neural network mediate body weight regulation2014

    • Author(s)
      Tetsuya Yamada, Sohei Tsukita, Hideki Katagiri
    • Organizer
      The 91st Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Kagoshima
    • Related Report
      2013 Final Research Report
  • [Presentation] 臓器間ネットワークからみた肥満・2型糖尿病2014

    • Author(s)
      山田 哲也、片桐 秀樹
    • Organizer
      第48回糖尿病学の進歩
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Inter-organ neural network media te body weight regulation.2014

    • Author(s)
      Tetsuya Yamada, Sohei Tsukita, Hideki Katagiri
    • Organizer
      The 91st Annual Meeting of the Physiological Society of Japan.
    • Place of Presentation
      Kagoshima
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 臓器間神経ネットワークによる体重調節機構の解明(日本肥満学会学術奨励賞受賞講演)2013

    • Author(s)
      山田哲也
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Year and Date
      2013-10-12
    • Related Report
      2013 Final Research Report
  • [Presentation] 肝からの臓器間ネットワークによるエネルギー代謝制御2013

    • Author(s)
      山田哲也、突田壮平、岡芳知、片桐秀樹
    • Organizer
      第56回日本糖尿病学会年次学術集会シンポジウム10:糖代謝と肝臓
    • Place of Presentation
      熊本市
    • Year and Date
      2013-05-17
    • Related Report
      2013 Final Research Report
  • [Presentation] 臓器間相互作用が司る糖代謝とエネルギー代謝のクロストーク2013

    • Author(s)
      山田哲也
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本市(日本糖尿学会学会賞(リリー賞)受賞講演)
    • Year and Date
      2013-05-16
    • Related Report
      2013 Final Research Report
  • [Presentation] 臓器間相互作用が司る糖代謝とエネルギー代謝のクロストーク2013

    • Author(s)
      山田 哲也
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 肝からの臓器間ネットワークによるエネルギー代謝制御2013

    • Author(s)
      山田 哲也
    • Organizer
      第56回日本糖尿病学会年次学術集会
    • Place of Presentation
      熊本
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 臓器間神経ネットワークによる体重調節機構の解明2013

    • Author(s)
      山田 哲也
    • Organizer
      第34回日本肥満学会
    • Place of Presentation
      東京
    • Related Report
      2013 Annual Research Report
    • 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(シンポジウム1:臓器間ネットワークによる心血管内分泌代謝調節)
    • Place of Presentation
      東京
    • Year and Date
      2012-11-24
    • Related Report
      2013 Final Research Report
  • [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シンポジウム14:中枢と末梢の機能調節連関
    • Place of Presentation
      名古屋市
    • Year and Date
      2012-04-21
    • Related Report
      2013 Final Research Report
  • [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
    • Related Report
      2012 Research-status Report
    • 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
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 褐色脂肪組織における熱産生抑制につながる組織間ネットワーク

    • Author(s)
      突田壮平、山田哲也 et al
    • Organizer
      第54回日本糖尿病学会年次学術集会
    • Place of Presentation
      札幌
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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