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Establishing appetitive vagal afferent nerve for ameliorating anorexia, frailty, cancer and depression

Research Project

Project/Area Number 19K22611
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 52:General internal medicine and related fields
Research Institution株式会社関西メディカルネット(関西電力医学研究所)

Principal Investigator

Yada Toshihiko  株式会社関西メディカルネット(関西電力医学研究所), 統合生理学研究センター統合生理学研究部, 部長 (60166527)

Co-Investigator(Kenkyū-buntansha) 岩崎 有作  京都府立大学, 生命環境科学研究科, 教授 (60528420)
Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2020: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords食欲不振 / フレイル / 漢方薬 / 玉ねぎ / 弓状核 / 抗がん剤 / neuropeptide Y / グレリン / 人参養栄湯 / イソアリイン / 認知機能 / 不安 / 摂食 / Neuropeptide Y / 視床下部弓状核 / Caチャネル / 認知 / 抗ガン剤 / 求心性迷走神経 / がん / 食欲促進性求心性迷走神経 / 食材
Outline of Research at the Start

食欲不振を成因または病態とする疾患に、うつ・ストレス性疾患、がん悪液質・抗がん剤投与、高齢者を中心としたサルコペニア・フレイルがある。食欲不振が改善すればこれらの病態は改善し、QOLが向上するが、有効な治療法はない。申請者は、食欲促進因子のグレリンと低血糖により活性化される求心性迷走神経細胞を観察し、新規の求心性迷走神経<食欲促進>サブクラスを想定した。本研究では、本サブクラスの活性化による食欲不振の改善を検証し、サルコペニア・フレイルの改善に繋がるかを検討する。さらに、<食欲促進>サブクラス神経細胞を活性化する分子群を探索し、選択的な活性化リガンド開発の基盤を得る。

Outline of Final Research Achievements

This study explored the substances and body’s systems that ameliorate anorexia and frailty. Ninjin’yoeito, a Kampo medicine, ameliorated anorexia in the mice treated with anti-cancer medicine, and increased food intake during active phase in normal mice. Ninjin’yoeito potently activated the neuropeptide Y (NPY) neurons and ghrelin-responsive neurons in the hypothalamic arcuate nucleus (ARC) via N-type Ca2+ channels, while its effect on the vagal afferent neurons was weak. Ninjin’yoeito elevated cognitive function, reduced anxiety, and enlarged life span in old mice, showing anti-frailty action.
Isoalliin, a major compoment of onion, also increased food intake during active phase and activated the ARC NPY neurons and ghrelin-responsive neurons.

Academic Significance and Societal Importance of the Research Achievements

高齢者、がん患者、抗がん剤の食欲不振、フレイルは現代社会の大きな問題であるが、有効な治療法がない。食欲不振、フレイルを改善する物質と生体系の探索を目指した。
漢方薬の人参養栄湯は、抗ガン剤投与マウスの食欲不振を改善し、高齢マウスの認知機能改善、不安軽減、寿命延伸をもたらし、フレイル改善作用を示した。人参養栄湯と玉ねぎ成分イソアリインは、正常マウスの活動期の摂食を増加させ、視床下部弓状核のNeuropeptide Y 神経及びグレリン応答性神経(食欲形成に中心的な役割を担う神経)を強力に活性化した。人参養栄湯の単独および食品併用による、食欲神経活性化と食欲不振・フレイル改善が期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (23 results)

All 2023 2022 2021 2020 2019

All Journal Article (12 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 12 results,  Open Access: 12 results) Presentation (6 results) (of which Int'l Joint Research: 2 results,  Invited: 4 results) Book (5 results)

  • [Journal Article] D-Allulose cooperates with glucagon-like peptide-1 and activates proopiomelanocortin neurons in the arcuate nucleus and central injection inhibits feeding in micesecretion.2023

    • Author(s)
      Rakhat Yermek, Lei Wang, Kentaro Kaneko, Wanxin Han, Yutaka Seino, Daisuke Yabe, Toshihiko Yada
    • Journal Title

      Biochem Biophys Res Commun

      Volume: -

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Status of ghrelin as an islet hormone and paracrine/autocrine regulator of insulin secretion2022

    • Author(s)
      Dezaki Katsuya、Yada Toshihiko
    • Journal Title

      Peptides

      Volume: 148 Pages: 170681-170681

    • DOI

      10.1016/j.peptides.2021.170681

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Onion component, isoalliin, stimulates feeding and activates the arcuate nucleus neuropeptide Y, ghrelin- and Ninjin’yoeito-responsive neurons.2021

    • Author(s)
      Wang L, Han W, Iwasaki Y, Yermek R, Sharp GW, Seino Y, Yada T.
    • Journal Title

      Neuropeptides

      Volume: 89 Pages: 102180-102180

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ninjin'yoeito targets distinct Ca2+ channels to activate ghrelin-responsive vs. unresponsive NPY neurons in the arcuate nucleus.2020

    • Author(s)
      Goswami Chayon, Dezaki Katsuya, Wang Lei, Inui Akio, Seino Yutaka, Yada Toshihiko
    • Journal Title

      Frontiers in Nutrition

      Volume: 7 Pages: 1-10

    • DOI

      10.3389/fnut.2020.00104

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The liver-brain-gut neural arc maintains the Treg cell niche in the gut2020

    • Author(s)
      Teratani T, Mikami Y, Nakamoto N, Suzuki T, Harada Y, Okabayashi K, Hagihara Y, Taniki N, Kohno K, Sibata S, Miyamoto K, Ishigame H, Chu Po-Sung, Sujino T, Suda W, Hattori M, Matsui M, Okada T, Okano H, Inoue M, Yada T, Kitagawa Y, Yoshimura A, Tanida M, Tsuda M, Iwasaki Y, Kanai T.
    • Journal Title

      Nature

      Volume: 585 Issue: 7826 Pages: 591-596

    • DOI

      10.1038/s41586-020-2425-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Peripheral circadian rhythms in the liver and white adipose tissue of mice are attenuated by constant light and restored by time-restricted feeding2020

    • Author(s)
      Yamamuro Daisuke、Takahashi Manabu、Nagashima Shuichi、Wakabayashi Tetsuji、Yamazaki Hisataka、Takei Akihito、Takei Shoko、Sakai Kent、Ebihara Ken、Iwasaki Yusaku、Yada Toshihiko、Ishibashi Shun
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 6 Pages: e0234439-e0234439

    • DOI

      10.1371/journal.pone.0234439

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lavender Oil Reduces Depressive Mood in Healthy Individuals and Enhances the Activity of Single Oxytocin Neurons of the Hypothalamus Isolated from Mice: A Preliminary Study2020

    • Author(s)
      Ogata Keizaburo、Ataka Koji、Suzuki Hajime、Yagi Takakazu、Okawa Ayumi、Fukumoto Takamasa、Zhang Boyang、Nakata Masanori、Yada Toshihiko、Asakawa Akihiro
    • Journal Title

      Evidence-Based Complementary and Alternative Medicine

      Volume: 2020 Issue: 1 Pages: 1-9

    • DOI

      10.1155/2020/5418586

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ninjin-yoeito activates ghrelin-responsive and unresponsive NPY neurons in the arcuate nucleus and counteracts cisplatin-induced anorexia2019

    • Author(s)
      Goswami Chayon、Dezaki Katsuya、Wang Lei、Inui Akio、Seino Yutaka、Yada Toshihiko
    • Journal Title

      Neuropeptides

      Volume: - Pages: 58-64

    • DOI

      10.1016/j.npep.2019.03.001

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Islet β-cell-produced NUCB2/nesfatin-1 maintains insulin secretion and glycemia along with suppressing UCP-2 in β-cells.2019

    • Author(s)
      Yang Y, Zhang B, Nakata M, Nakae J, Mori M, Yada T.
    • Journal Title

      J Physiol Sci.

      Volume: 69 Issue: 5 Pages: 733-739

    • DOI

      10.1007/s12576-019-00689-2

    • NAID

      40022006462

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Central Glucagon-like Peptide-1 Receptor Signaling via Brainstem Catecholamine Neurons Counteracts Hypertension in Spontaneously Hypertensive Rats.2019

    • Author(s)
      Katsurada K, Nakata M, Saito T, Zhang B, Maejima Y, Nandi SS, Sharma NM, Patel KP, Kario K, Yada T
    • Journal Title

      Sci Rep.

      Volume: 19 Issue: 1 Pages: 12986-12986

    • DOI

      10.1038/s41598-019-49364-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Relay of peripheral oxytocin to central oxytocin neurons via vagal afferents for regulating feeding.2019

    • Author(s)
      Iwasaki Y, Kumari P, Wang L, Hidema S, Nishimori K, Yada T.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 519(3) Issue: 3 Pages: 553-558

    • DOI

      10.1016/j.bbrc.2019.09.039

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nesfatin-1 ameliorates type-2 diabetes-associated reproductive dysfunction in male mice.2019

    • Author(s)
      Ranjan A, Choubey M, Yada T, Krishna A.
    • Journal Title

      J Endocrinol Invest.

      Volume: 43(4) Issue: 4 Pages: 515-528

    • DOI

      10.1007/s40618-019-01136-0

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] NPYによる室傍核オキシトシン神経シナプス制御の機序と絶食後過食の仲介2021

    • Author(s)
      王磊,須山成朝,矢田俊彦
    • Organizer
      第41回日本肥満学会/第38回日本肥満症治療学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] Intestinal GLP-1 release by oral administration of rare sugar D-alluloseameliorates arrhythmic-overeating and obesity via vagal afferents.2019

    • Author(s)
      Yusaku Iwasaki and Toshihiko Yada
    • Organizer
      NIPS International Workshop “Sensing food/nutrient/environment toward integrative metabolic regulation
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] D-Allulose, a novel GLP-1 releaser, effectively and safely corrects hyperglycemia.2019

    • Author(s)
      Toshihiko Yada
    • Organizer
      Rare Sugar Congress 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 希少糖D-アルロースによるGLP-1シグナリングと肥満・糖尿病の改善2019

    • Author(s)
      矢田俊彦
    • Organizer
      かがわ糖質バイオフォーラム第11回シンポジウム
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 希少糖アルロースによる内因性GLP-1放出と肥満・糖尿病改善の特徴2019

    • Author(s)
      矢田俊彦
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] GLP-1 放出因子 D-アルロースとGLP-1受容体作動薬の血糖降下作用の相違2019

    • Author(s)
      矢田俊彦
    • Organizer
      第62回日本糖尿病学会年次学術集会
    • Related Report
      2019 Research-status Report
  • [Book] 標準生理学2019

    • Author(s)
      矢田俊彦
    • Total Pages
      1202
    • Publisher
      医学書院
    • ISBN
      9784260034296
    • Related Report
      2019 Research-status Report
  • [Book] Diabetes Strategy2019

    • Author(s)
      矢田俊彦、岩﨑有作
    • Total Pages
      100
    • Publisher
      株式会社先端医学社
    • Related Report
      2019 Research-status Report
  • [Book] 生化学2019

    • Author(s)
      矢田俊彦、岩﨑有作
    • Total Pages
      140
    • Publisher
      公益社団法人 日本生化学会
    • Related Report
      2019 Research-status Report
  • [Book] 内分泌・糖尿病・代謝内科2019

    • Author(s)
      岩﨑有作、矢田俊彦
    • Total Pages
      130
    • Publisher
      科学評論社
    • Related Report
      2019 Research-status Report
  • [Book] メディカル・サイエンス・ダイジェスト2019

    • Author(s)
      矢田俊彦、岩﨑有作
    • Total Pages
      62
    • Publisher
      ニューサイエンス社
    • Related Report
      2019 Research-status Report

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Published: 2019-07-04   Modified: 2023-01-30  

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