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Identification of molecular mechanisms of inter-organ neuronal network in body weight regulation

Research Project

Project/Area Number 26293215
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-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, 准教授 (90400374)

Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2016: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywordsエネルギー代謝 / 神経 / エネルギー代謝調節 / 臓器間相互作用 / 体重調節 / 自律神経
Outline of Final Research Achievements

We previously demonstrated that afferent neuronal signals are transmitted to the brain according to alterations in fat accumulation in the liver thereby enhancing energy expenditure in brown adipose tissue (BAT). On the other hand, we recently identified a novel positive-feedback system for promoting weight gain by suppressing energy expenditure in BAT when there are sign of energy abundance in the liver. The aim of this study was to detect particular molecule that is responsible for initiating afferent neuronal signal at the liver. A comprehensive screening with mass spectrometry revealed two peptides and one metabolite that could be such candidates, but after further experiments, we found out that neither of them was actually involved in the neuronal network connecting the liver and systemic energy metabolism. These results suggest that substance (s) other than peptides or metabolites might initiate the neural network at the liver.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (38 results)

All 2018 2017 2016 2015 2014 Other

All Journal Article (21 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 17 results,  Open Access: 16 results,  Acknowledgement Compliant: 5 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 11 results) Remarks (1 results)

  • [Journal Article] Olfactory receptors are expressed in pancreatic β-cells and promote glucose-stimulated insulin secretion2018

    • Author(s)
      Munakata Y, Yamada T, Imai J, Takahashi K, Tsukita S, Shirai Y, Kodama S, Asai Y, Sugisawa T, Chiba Y, Kaneko K, Uno K, Sawada S, Hatakeyama H, Kanzaki M, Miyazaki JI, Oka Y, Katagiri H
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1499-1499

    • DOI

      10.1038/s41598-018-19765-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronal signals regulate obesity induced β-cell proliferation by FoxM1 dependent mechanism2017

    • Author(s)
      Yamamoto J, Imai J, Izumi T, Takahashi H, Kawana Y, Takahashi K, Kodama S, Kaneko K, Gao J, Uno K, Sawada S, Asano T, Kalinichenko VV, Susaki EA, Kanzaki M, Ueda HR, Ishigaki Y, Yamada T, Katagiri H
    • Journal Title

      Nature Communications

      Volume: 8 Issue: 1 Pages: 1930-1930

    • DOI

      10.1038/s41467-017-01869-7

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Common Hepatic Branch of Vagus Nerve-Dependent Expression of Immediate Early Genes in the Mouse Brain by Intraportal L-Arginine: Comparison with Cholecystokinin-8.2017

    • Author(s)
      Yamada D, Koppensteiner P, Odagiri S, Eguchi M, Yamaguchi S, Yamada T, Katagiri H, Wada K, Sekiguchi M.
    • Journal Title

      Front Neurosci.

      Volume: 11 Pages: 1-10

    • DOI

      10.3389/fnins.2017.00366

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of the activations of three major hepatic Akt substrates on glucose metabolism in male mice.2017

    • Author(s)
      Sakai G, Inoue I, Suzuki T, Sumita T, Inukai K, Katayama S, Awata T, Yamada T, Asano T, Katagiri H, Noda M, Shimada A, Ono H.
    • Journal Title

      Endocrinology.

      Volume: 158 Issue: 8 Pages: 2659-2671

    • DOI

      10.1210/en.2016-1969

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Metformin Directly Binds the Alarmin HMGB1 and Inhibits its Proinflammatory Activity.2017

    • Author(s)
      Horiuchi T, Sakata N, Narumi Y, Kimura T, Hayashi T, Nagano K, Liu K, Nishibori M, Tsukita S, Yamada T, Katagiri H, Shirakawa R, Horiuchi H.
    • Journal Title

      J Biol Chem.

      Volume: 印刷中 Issue: 20 Pages: 8436-8446

    • DOI

      10.1074/jbc.m116.769380

    • NAID

      120006331939

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Knockout of Vasohibin-1 Gene in Mice Results in Healthy Longevity with Reduced Expression of Insulin Receptor, Insulin Receptor Substrate 1, and Insulin Receptor Substrate 2 in Their White Adipose Tissue.2017

    • Author(s)
      Takeda E, Suzuki Y, Yamada T, Katagiri H, Sato Y.
    • Journal Title

      J Aging Res.

      Volume: 2017 Pages: 1-11

    • DOI

      10.1155/2017/9851380

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sodium-Glucose Cotransporter 2 Inhibitor Improves Complications of Lipodystrophy: A Case Report.2017

    • Author(s)
      Kawana Y, Imai J, Sawada S, Yamada T, Katagiri H.
    • Journal Title

      Ann Intern Med.

      Volume: 166 Pages: 450-451

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Activation of the Hypoxia Inducible Factor 1α Subunit Pathway in Steatotic Liver Contributes to Formation of Cholesterol Gallstones2017

    • Author(s)
      Asai Y, Yamada T, Tsukita S, Takahashi K, Maekawa M, Honma M, Ikeda M, Murakami K, Munakata Y, Shirai Y, Kodama S, Sugisawa T, Chiba Y, Kondo Y, Kaneko K, Uno K, Sawada S, Imai J, Nakamura Y, Yamaguchi H, Tanaka K, Sasano H, Mano N, Ueno Y, Shimosegawa T, Katagiri H
    • Journal Title

      Gastroenterology

      Volume: 152 Issue: 6 Pages: 1521

    • DOI

      10.1053/j.gastro.2017.01.001

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ER Stress Protein CHOP Mediates Insulin Resistance by Modulating Adipose Tissue Macrophage Polarity2017

    • Author(s)
      Suzuki T, Gao J, Ishigaki Y, Kondo K, Sawada S, Izumi T, Uno K, Kaneko K, Tsukita S, Takahashi K, Asao A, Ishii N, Imai J, Yamada T, Oyadomarai S, Katagiri H
    • Journal Title

      Cell Rep

      Volume: 18 Issue: 8 Pages: 2045

    • DOI

      10.1016/j.celrep.2017.01.076

    • NAID

      120007001421

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] マイクロRNAと糖尿病2017

    • Author(s)
      山田哲也、片桐秀樹
    • Journal Title

      DIABETS JOURNAL

      Volume: 45 Pages: 124-130

    • Related Report
      2017 Annual Research Report
  • [Journal Article] 肥満のメカニズム-なぜ太るのか2017

    • Author(s)
      山田哲也、片桐秀樹
    • Journal Title

      成人病と生活習慣病

      Volume: 47 Pages: 1356-1361

    • Related Report
      2017 Annual Research Report
  • [Journal Article] microRNA-106bとmicroRNA-222は膵β細胞の増殖促進を介して、インスリン分泌低下による糖尿病を改善する.2017

    • Author(s)
      山田哲也、突田壮平、片桐秀樹
    • Journal Title

      Diabetes Update

      Volume: 6 Pages: 16-18

    • Related Report
      2017 Annual Research Report
  • [Journal Article] MicroRNAs 106b and 222 Improve Hyperglycemia in a Mouse Model of Insulin-Deficient Diabetes via Pancreatic β-Cell Proliferation2016

    • Author(s)
      Tsukita S, Yamada T, Takahashi K, Munakata Y, Hosaka S, Takahashi H, Gao J, Shirai Y, Kodama S, Asai Y, Sugisawa T, Chiba Y, Kaneko K, Uno K, Sawada S, Imai J, Katagiri H
    • Journal Title

      EBioMedicine

      Volume: 15 Pages: 163

    • DOI

      10.1016/j.ebiom.2016.12.002

    • NAID

      130007811669

    • URL

      https://pure.teikyo.jp/en/publications/297babbe-b305-4608-9a87-29fa0a000d06

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] エネルギー代謝調節における臓器間神経ネットワークの役割2016

    • Author(s)
      山田哲也
    • Journal Title

      日本薬理学雑誌

      Volume: 148 Pages: 28-33

    • NAID

      130005164794

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, acutely reduces energy expenditure in BAT via neural signals in mice2016

    • Author(s)
      Yumiko Chiba, Tetsuya Yamada, Sohei Tsukita, Kei Takahashi, Yuichiro Munakata, Yuta Shirai, Shinjiro Kodama, Yoichiro Asai, Takashi Sugisawa, Kenji Uno, Shojiro Sawada, Junta Imai, Kazuhiro Nakamura, Hideki Katagiri
    • Journal Title

      PLOS ONE

      Volume: 11 Issue: 3 Pages: e0150756-e0150756

    • DOI

      10.1371/journal.pone.0150756

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Maternal dietary imbalance between omega-6 and omega-3 polyunsaturated fatty acids impairs neocortical development via epoxy metabolites2016

    • Author(s)
      Sakayori N, Kikkawa T, Tokuda H, Kiryu E, Yoshizaki K, Kawashima H, Yamada T, Arai H, Kang JX, Katagiri H, Shibata H, Innis SM, Arita M, Osumi N.
    • Journal Title

      Stem Cells.

      Volume: 34 Issue: 2 Pages: 470

    • DOI

      10.1002/stem.2246

    • URL

      https://pure.teikyo.jp/en/publications/0a44dab9-77bc-49b5-a056-a4cdd3e66a1d

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Impacts of the Great East Japan Earthquake on diabetic patients2015

    • Author(s)
      anaka M, Imai J, Satoh M, Hashimoto T, Izumi T, Sawada S, Uno K, Hasegawa Y, Kaneko K, Yamada T, Ishigaki Y, Imai Y and Katagiri H.
    • Journal Title

      J Diabetes Invest.

      Volume: 6 Issue: 5 Pages: 577

    • DOI

      10.1111/jdi.12336

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals2015

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

      Nat Commun

      Volume: 6 Issue: 1 Pages: 7940-7940

    • DOI

      10.1038/ncomms8940

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rho-Kinase Inhibition Ameliorates Metabolic Disorders through Activation of AMPK Pathway in Mice2014

    • Author(s)
      Noda K, Nakajima S, Godo S, Saito H, Ikeda S, Shimizu T, Enkhjargal B, Fukumoto Y, Tsukita S, Yamada T, Katagiri H, Shimokawa H.
    • Journal Title

      PLoS One

      Volume: 9(11) Issue: 11 Pages: e110446-e110446

    • DOI

      10.1371/journal.pone.0110446

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Glycemic control in diabetic patients with impaired endogenous insulin secretory capacity is vulnerable after a natural disaster: Study of great east Japan earthquake2014

    • Author(s)
      Tanaka M, Imai J, Satoh M, Hashimoto T, Izumi T, Sawada S, Uno K, Hasegawa Y, Kaneko K, Yamada T, Ishigaki Y, Imai Y, Katagiri H
    • Journal Title

      Diabetes Care

      Volume: 37 Issue: 10 Pages: e212-e213

    • DOI

      10.2337/dc14-1479

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Simultaneous copy number losses within multiple subtelomeric regions in early-onset type2 diabetes mellitus2014

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

      PLoS One

      Volume: 9 Issue: 4 Pages: e88602-e88602

    • DOI

      10.1371/journal.pone.0088602

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] microRNAによる膵β細胞の増殖制御2018

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第32回 日本糖尿病・肥満動物学会年次学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 中枢末梢臓器連関を介したSGLT2阻害薬によるエネルギー代謝調節機構2017

    • Author(s)
      山田哲也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台(仙台国際センター)
    • Year and Date
      2017-03-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] 肥満症の病態形成における肝臓からの臓器連関の役割2017

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第53回高血圧関連疾患モデル学会学術総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 膵β細胞老化における血管内皮の役割2017

    • Author(s)
      山田哲也、高橋広延、宗像佑一郎、突田壮平、片桐秀樹
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 臓器連関から肥満症の病態・治療を考える2017

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第27回日本病態生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肥満症の病態形成における肝臓からの臓器連関の役割2016

    • Author(s)
      山田哲也 片桐秀樹
    • Organizer
      第39回 日本分子生物学会年会
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] Role of the inter-organ neural network from the liver in systemic energy metabolism.2016

    • Author(s)
      Tetsuya Yamada, Hideki katagiri.
    • Organizer
      The 39th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      横浜(パシフィコ横浜)
    • Year and Date
      2016-07-20
    • Related Report
      2016 Annual Research Report
  • [Presentation] Role of the inter-organ network from the liver in systemic energy metabolism.2016

    • Author(s)
      Tetsuya Yamada, Hideki katagiri.
    • Organizer
      The 59th Annual Meeting of the Japanese Diabetes Society
    • Place of Presentation
      京都(国立京都国際会館)
    • Year and Date
      2016-05-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 個体レベルのエネルギー代謝調節における肝臓の役割-臓器間神経ネットワークの観点から-2016

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜 会議センター(神奈川県横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 個体レベルのエネルギー代謝調節における肝臓の役割-臓器間神経ネットワークの観点から-2015

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第38回日本高血圧学会総会
    • Place of Presentation
      愛媛県県民文化会館(愛媛県松山市)
    • Year and Date
      2015-10-09
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Inter-organ neural network mediate the regulation of systemic energy metabolism2015

    • Author(s)
      Tetsuya Yamada, Hideki Katagiri
    • Organizer
      The 36th Annual Meeting of Japan Society for the Study of Obesity, The 46th NIPS International Symposium
    • Place of Presentation
      名古屋国際会議場(愛知県名古屋市)
    • Year and Date
      2015-10-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 体重調節における臓器連関の役割-なぜ太りやすく痩せにくいのか-2015

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第58回日本糖尿病学会年次学術集会
    • Place of Presentation
      海峡メッセ下関(山口県下関市)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] エネルギー代謝調節における臓器間神経ネットワーク機構の役割2015

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第88回 日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(名古屋市)
    • Year and Date
      2015-03-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 糖・エネルギー代謝と臓器ネットワーク2015

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第49回 糖尿病学の進歩
    • Place of Presentation
      ホテルグランヴィア岡山(岡山市)
    • Year and Date
      2015-02-21
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 臓器間神経ネットワークによる糖・エネルギー代謝調節機構の解明2015

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第44回 日本心脈管作動物質学会
    • Place of Presentation
      高松センタービル(高松市)
    • Year and Date
      2015-02-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] エネルギー代謝における臓器間相互作用2014

    • Author(s)
      山田哲也、片桐秀樹
    • Organizer
      第87回 日本内分泌学会学術総会
    • Place of Presentation
      福岡国際会議場(福岡市)
    • Year and Date
      2014-04-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Remarks] 東北大学大学院医学系研究科 糖尿病代謝内科学分野

    • URL

      http://www.diabetes.med.tohoku.ac.jp/

    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2019-03-29  

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