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Establishment of the animal model of sarcopenia caused by metabolic disorders like as humans

Research Project

Project/Area Number 20K21750
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionUniversity of Yamanashi

Principal Investigator

Mochizuki Kazuki  山梨大学, 大学院総合研究部, 教授 (80423838)

Co-Investigator(Kenkyū-buntansha) 安藤 隆  山梨大学, 大学院総合研究部, 講師 (10377492)
田中 佑治  山梨大学, 大学院総合研究部, 特任准教授 (40625513)
Project Period (FY) 2020-07-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2022: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsBrd4 / サルコペニア / 中鎖脂肪 / Brd4ヘテロ欠損マウス / 筋合成 / 筋分解 / サルコペニアモデル / BRD4 / 骨格筋 / 老齢モデル / BRD4ヘテロ欠損マウス / バイオマーカー
Outline of Research at the Start

以下のように、食品・医薬品によるサルコペニア改善を評価しうる“代謝異常に起因するサルコペニア動物モデル”を世界に先駆けて樹立することを目的とする。
1.代謝異常からサルコペニアを呈するモデル(Brd4ヘテロ欠損マウス)の検証
2.中鎖脂肪によるサルコペニア改善効果の検証
3.サルコペニア動物モデルの妥当性をヒトで評価できるバイオマーカーの探索・検証

Outline of Final Research Achievements

In this study, we found that aged Brd4 heterozygous mice exhibited lower grip strength and lower organ weights (liver, epididymal fat and skeletal muscle) compared with wild type mice. Feeding Brd4 heterozygous mice caprylic acid (C8) for about 5 months enhanced expression of genes related to glycolytic side pathway, citric acid cycle, and lipid droplet degradation and muscle regeneration (Myh3), in the gastrocnemius muscle. In soleus muscle, feeding the caprylic acid decreased expression of muscle degradation genes (Atrogin1, Murf1) and increased expression of protein synthesis-related genes (Rpl32, Rps21). Similar results with increased grip strength were observed in feeding caprylic acid (C10). Together, the Brd4 heterozygous mouse could be used as a sarcopenia model.

Academic Significance and Societal Importance of the Research Achievements

学術的意義は、エネルギー代謝を促進するBRD4のヘテロ欠損マウスが、サルコペニアモデルとして使用可能であること、中鎖脂肪は、サルコペニアの予防に有効であることを示したことである。
社会的意義は、Brd4ヘテロ欠損マウスを用いてサルコペニアを予防・治療しうる食品因子、医薬品の研究開発が促進されることである。さらに、食品因子、医薬品の研究開発を促進することによって、高齢者でも元気に生活できる社会に貢献することである。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (42 results)

All 2023 2022 2021 2020

All Journal Article (22 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 17 results,  Open Access: 17 results) Presentation (20 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results)

  • [Journal Article] Dietary protein restriction during pregnancy and/or early weaning reduces the number of goblet cells in the small and large intestines of female mice pups2023

    • Author(s)
      Adachi H, Ishiyama S, Mochizuki K
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 34 Pages: 101475-101475

    • DOI

      10.1016/j.bbrep.2023.101475

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Medium-Chain Triglycerides Reduce Glomerulosclerosis and Induce Redox Genes Level of NSY Mice with Diabetic Nephropathy2023

    • Author(s)
      Hagiwara M, Ishiyama S, Mochizuki K
    • Journal Title

      Pharmanutrition

      Volume: 23 Pages: 100325-100325

    • DOI

      10.1016/j.phanu.2022.100325

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Decreased postprandial glucose and insulin secretion after co-ingestion of barley mixed rice with yam paste in healthy Japanese participants: a randomized crossover trial2023

    • Author(s)
      Matsuoka T, Yamaji A, Kurosawa C, Shinohara M, Takayama I, Nakagomi H, Izumi K, Ichikawa Y, Hariya N, Mochizuki K
    • Journal Title

      Asia Pacific Journal of Clinical Nutrition.

      Volume: -

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal protein intake in early pregnancy and child development at age 3 years2023

    • Author(s)
      Miyake Kunio、Mochizuki Kazuki、Kushima Megumi、Shinohara Ryoji、Horiuchi Sayaka、Otawa Sanae、Akiyama Yuka、Ooka Tadao、Kojima Reiji、Yokomichi Hiroshi、Yamagata Zentaro、Japan Environment and Children’s Study Group
    • Journal Title

      Pediatric Research

      Volume: 2023 Issue: 1 Pages: 392-399

    • DOI

      10.1038/s41390-022-02435-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Supra-Multifactorial Survey YHAB revealed Highly Prevalent Sleep Apnoea Syndrome in Unaware Older Adults and Potential Combinatorial Factors for Its Initial Screening.2022

    • Author(s)
      Tanaka Y, Ando T, Mochizuki K, Igarashi S, Tsuchiya K, Saito K, Ito Y, Yamagata Z, Iwasaki M, YHAB Health Group.
    • Journal Title

      Supra-Multifactorial Survey YHAB revealed Highly Prevalent Sleep Apnoea Syndrome in Unaware Older Adults and Potential Combinatorial Factors for Its Initial Screening.

      Volume: -

    • DOI

      10.3389/fragi.2022.965199

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 大麦摂取は2型糖尿病患者の血清尿酸高値を低下させる2022

    • Author(s)
      遅野井健,道口佐多子,久賀なつみ,横田由夏,飛田春菜,大渕健介,斎藤三代子,丸山聡子,望月和樹,加藤誠
    • Journal Title

      診療と新薬

      Volume: 59(8) Pages: 435-443

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] β-Carotene enhances the expression of inflammation-related genes and histone H3 K9 acetylation, K4 dimethylation, and K36 trimethylation around these genes in juvenile macrophage-like THP-1 cells2022

    • Author(s)
      Kondo S, Suzuki R, Nakashima Y, Mochizuki K
    • Journal Title

      Biochemistry and Biophysics Reports.

      Volume: 31 Pages: 2022-2022

    • DOI

      10.1016/j.bbrep.2022.101325

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] From lessons on the long-term effects of the preimplantation environment on later health to a "modified ART-DOHaD" animal model.2022

    • Author(s)
      Bari MW, Ishiyama S, Matsumoto S, Mochizuki K and Kishigami S
    • Journal Title

      Reprod Med Biol.

      Volume: 21(1) Issue: 1

    • DOI

      10.1002/rmb2.12469

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protein restriction during the fetal period upregulates IL1B and IL13 while suppressing MUC2 expression in the jejunum of mice after weaning2022

    • Author(s)
      Adachi H, Ishiyama S, Mochizuki K
    • Journal Title

      Nutrition

      Volume: 98 Pages: 111605-111605

    • DOI

      10.1016/j.nut.2022.111605

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparative Analysis of Gene Expression Profiles in the Adipose Tissue of Obese Adult Mice With Rapid Infantile Growth After Undernourishment In Utero2022

    • Author(s)
      Suzuki Misako、Kohmura-Kobayashi Yukiko、Ueda Megumi、Furuta-Isomura Naomi、Matsumoto Masako、Oda Tomoaki、Kawai Kenta、Itoh Toshiya、Matsuya Madoka、Narumi Megumi、Tamura Naoaki、Uchida Toshiyuki、Mochizuki Kazuki、Itoh Hiroaki
    • Journal Title

      Frontiers in Endocrinology

      Volume: 13 Pages: 818064-818064

    • DOI

      10.3389/fendo.2022.818064

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Medium-chain fatty acids enhance expression and histone acetylation of genes related to lipid metabolism in insulin-resistant adipocytes2022

    • Author(s)
      Kawamura Musashi、Goda Naoki、Hariya Natsuyo、Kimura Mayu、Ishiyama Shiori、Kubota Takeo、Mochizuki Kazuki
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 29 Pages: 101196-101196

    • DOI

      10.1016/j.bbrep.2021.101196

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 着床前胚の体外培養とその長期影響~挑戦と課題、そして応用~“Embryo culture and long-term consequences: challenges, new issues, and applications”.2021

    • Author(s)
      松本沙知, 石山詩織,望月和樹,岸上哲士
    • Journal Title

      動物細胞培養における培地と培養系の工夫 ~技術と市場~,

      Volume: -

    • Related Report
      2021 Research-status Report
  • [Journal Article] 発達期環境によるサイトカインストーム形成と動脈硬化関連疾患発症との関連“Relationship between cytokine storm triggered by environments during developing stages and arteriosclerosis-related diseases”2021

    • Author(s)
      石山詩織,岸上哲士, 望月和樹
    • Journal Title

      BIO Clinica

      Volume: -

    • Related Report
      2021 Research-status Report
  • [Journal Article] Effects of barley intake on glycemic control in Japanese patients with type 2 diabetes mellitus undergoing antidiabetic therapy: a prospective study2021

    • Author(s)
      Osonoi Takeshi、Matsuoka Tsubasa、Ofuchi Kensuke、Katoh Makoto、Kobayashi Toshiki、Mochizuki Kazuki
    • Journal Title

      Diabetology International

      Volume: 13 Issue: 2 Pages: 387-395

    • DOI

      10.1007/s13340-021-00552-z

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of the Diabetic Kidney Disease Mouse Model Culturing Embryos in α-Minimum Essential Medium In Vitro, and Feeding Barley Diet Attenuated the Pathology2021

    • Author(s)
      Ishiyama Shiori、Kimura Mayu、Nakagawa Takao、Fujimoto Yuka、Uchimura Kohei、Kishigami Satoshi、Mochizuki Kazuki
    • Journal Title

      Frontiers in Endocrinology

      Volume: 12

    • DOI

      10.3389/fendo.2021.746838

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of Carbohydrate-Responsive Metabolic Genes by Histone Acetylation and the Acetylated Histone Reader BRD4 in the Gene Body Region2021

    • Author(s)
      Mochizuki Kazuki、Ishiyama Shiori、Hariya Natsuyo、Goda Toshinao
    • Journal Title

      Frontiers in Molecular Biosciences

      Volume: 8

    • DOI

      10.3389/fmolb.2021.682696

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Feeding Rats Medium-Chain Triglycerides and Tomato Powder Increases Liver Lycopene Content and Reduces the Expression of Genes Related to Lipid Metabolism in the Liver2021

    • Author(s)
      Kimura Mayu、Tamura Sayaka、Ishiyama Shiori、Mochizuki Kazuki
    • Journal Title

      ACS Food Science & Technology

      Volume: 1 Issue: 6 Pages: 993-1001

    • DOI

      10.1021/acsfoodscitech.0c00155

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Consumption of barley ameliorates the diabetic steatohepatitis and reduces the high transforming growth factor β expression in mice grown in α-minimum essential medium in vitro as embryos2021

    • Author(s)
      Ishiyama Shiori、Kimura Mayu、Umihira Nodoka、Matsumoto Sachi、Takahashi Atsushi、Nakagawa Takao、Wakayama Teruhiko、Kishigami Satoshi、Mochizuki Kazuki
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 27 Pages: 101029-101029

    • DOI

      10.1016/j.bbrep.2021.101029

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mice derived from in vitro αMEM-cultured preimplantation embryos exhibit postprandial hyperglycemia and higher inflammatory gene expression in peripheral leukocytes2021

    • Author(s)
      Ishiyama Shiori、Kimura Mayu、Umihira Nodoka、Matsumoto Sachi、Takahashi Atsushi、Nakagawa Takao、Wakayama Teruhiko、Kishigami Satoshi、Mochizuki Kazuki
    • Journal Title

      Bioscience, Biotechnology, and Biochemistry

      Volume: 85 Issue: 5 Pages: 1215-1226

    • DOI

      10.1093/bbb/zbab023

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] S100 Genes are Highly Expressed in Peripheral Leukocytes of Type 2 Diabetes Mellitus Patients Treated with Dietary Therapy2021

    • Author(s)
      Kondo Shinnosuke、Mochizuki Kazuki、Hariya Natsuyo、Saito Miyoko、Doguchi Satako、Osonoi Takeshi
    • Journal Title

      Drugs in R&D

      Volume: 21 Issue: 1 Pages: 91-101

    • DOI

      10.1007/s40268-020-00334-z

    • Related Report
      2020 Research-status Report
  • [Journal Article] Bromodomain-containing protein 4 regulates a cascade of lipid-accumulation-related genes at the transcriptional level in the 3T3-L1 white adipocyte-like cell line2020

    • Author(s)
      Mochizuki Kazuki、Yamada Masami、Inoue Takuya、Hariya Natsuyo、Kubota Takeo、Goda Toshinao
    • Journal Title

      European Journal of Pharmacology

      Volume: 883 Pages: 173351-173351

    • DOI

      10.1016/j.ejphar.2020.173351

    • Related Report
      2020 Research-status Report
  • [Journal Article] Glucose and TNF enhance expression of TNF and IL1B, and histone H3 acetylation and K4/K36 methylation, in juvenile macrophage cells2020

    • Author(s)
      Honma Kazue、Machida Chie、Mochizuki Kazuki、Goda Toshinao
    • Journal Title

      Gene: X

      Volume: 5 Pages: 100034-100034

    • DOI

      10.1016/j.gene.2020.100034

    • Related Report
      2020 Research-status Report
  • [Presentation] Protein restriction during the fetal period upregulates IL1B and IL13 while suppressing MUC2 expression in the jejunum of mice after weaning2022

    • Author(s)
      Adachi H、Kudo M、Ishiyama S、Mochizuki K,
    • Organizer
      22nd IUNS-International Congress of Nutrition
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Excessive folic acid supplementation in pregnant mice induces glucose and lipid metabolic disorders in their offspring in infancy and/or adulthood.2022

    • Author(s)
      Kintaka Y、Nakamura S、Wada N、Okuda A、Tanabe K、Mochizuki K、Oku T.
    • Organizer
      2nd IUNS-International Congress of Nutrition
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Relations between carbohydrate-responsive epigenetics and DOHaD2022

    • Author(s)
      Mochizuki K, Natsuyo N, Shiori I, Itoh H.
    • Organizer
      22nd IUNS-International Congress of Nutrition
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 中鎖脂肪は、2 型糖尿病 NSY マウスの腎症の 進展を抑制する2022

    • Author(s)
      萩原 麻衣、石山詩織、望月和樹
    • Organizer
      第 5 回中性脂肪学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胎生期タンパク質コリン低栄養マウスへのトマトパウダー投与が脂肪肝等の 代謝異常に与える影響2022

    • Author(s)
      岩崎三奈、石山詩織、望月和樹
    • Organizer
      第12回機能油脂懇話会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 中鎖脂肪とリコペン共投与が肝臓における糖・脂質代謝へ与える影響2022

    • Author(s)
      早川 俳人、石山詩織、望月和樹
    • Organizer
      第12回機能油脂懇話会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胚発生初期2細胞期胚へのαMEM培地の曝露および出生後の高脂肪食投与は産仔の脂肪肝および糖尿病性腎症を誘導する2022

    • Author(s)
      石山詩織、中川隆生、内村幸平、岸上哲士、望月和樹
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胎生期タンパク質制限が、出生後の 仔の腸バリア機能に与える影響2022

    • Author(s)
      足立遥郁、工藤美芙由、石山詩織、望月和樹
    • Organizer
      第9回 日本DOHaD学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 大腸由来上皮様細胞へのフラクトオリゴ糖投与が腸バリア機能関連遺伝子の発現に及ぼす影響2022

    • Author(s)
      原澤彩、石山詩織、望月和樹
    • Organizer
      第9回 日本DOHaD学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胎生期糖質制限による生後の代謝異常と大麦及び フラクトオリゴ糖摂取摂取による改善機構の解明2022

    • Author(s)
      山本裕昌 望月和樹
    • Organizer
      第9回 日本DOHaD学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 着床前胚の αMEM 培地暴露は,産仔マウス肝の脂肪滴形成遺伝子 Cidea 発現および同遺伝子周辺のヒス トンアセチル化を促進する2022

    • Author(s)
      石山詩織、中川隆生、岸上哲士、望月和樹
    • Organizer
      第65回日本糖尿病学会年次学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胎生期のタンパク質・重度コリン制限による脂肪肝発症と脂肪組織のインスリン感受性遺伝子発現との関連2022

    • Author(s)
      岩崎三奈、相澤友香、針谷夏代、平山訓子、宮本和子、望月和樹
    • Organizer
      第65回日本糖尿病学会年次学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒストンアセチル化修飾による脂肪滴蓄積遺伝子Cidea、CidecおよびPlin4の発現増大機構---胚環境操作により2型糖尿病-脂肪肝炎を呈するMEMマウスにおける検討---2022

    • Author(s)
      石山詩織、中川隆生、岸上哲士、望月和樹
    • Organizer
      第76回日本栄養・食糧学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 胎生期のタンパク質制限は、離乳後のマウスの空腸において、IL1B および IL13 の発現を 増大させ、MUC2 の発現を減少させる2022

    • Author(s)
      足立遥郁、工藤美芙由、石山 詩織、望月 和樹
    • Organizer
      第76回日本栄養・食糧学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 健康な後期高齢者 32 名中 16 名で疑われた睡眠時無呼吸症候群と罹患予測の可能性2022

    • Author(s)
      田中佑治、安藤隆、望月和樹、五十嵐賢、、YHAB研究グループ
    • Organizer
      第64回日本老年医学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 睡眠時無呼吸症候群の危険因子としてのロコモティブシンドローム-山梨健康長寿コホート Y-HALE study2022

    • Author(s)
      安藤隆、田中佑治、望月和樹、YHAB研究グループ
    • Organizer
      日本整形外科学会総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 然糖尿病モデルNSYマウスにおける中鎖脂肪とキサンチンオキシダーゼ阻害剤の糖尿病性腎症抑制効果の検証2021

    • Author(s)
      萩原 麻衣、望月和樹
    • Organizer
      糖尿病性腎症研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] グルコースによる糖、脂質代謝の攪乱と中鎖脂肪酸による改善 - HepG2 肝培養細胞による検討-2021

    • Author(s)
      萩原 麻衣、望月和樹
    • Organizer
      高尿酸血症・メタボリックシンドローム リサーチフォーラム 第 17 回 研究集会
    • Related Report
      2021 Research-status Report
  • [Presentation] 中鎖脂肪とトマトパウダーの共投与はラット肝臓におけるリコペン蓄積を増大させ、糖・脂質代謝関連遺伝子の発現を低下させる2021

    • Author(s)
      木村真由 田村 彩、望月 和樹
    • Organizer
      第11回機能油脂懇話会
    • Related Report
      2021 Research-status Report
  • [Presentation] 胎生期低栄養による糖・脂質代謝異常と中鎖脂肪による改善2021

    • Author(s)
      向井菫、山下紗輝、望月和樹
    • Organizer
      第10回日本DOHaD学会学術集会
    • Related Report
      2021 Research-status Report

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Published: 2020-08-03   Modified: 2024-01-30  

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