• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Novel therapeutic strategies for fatty liver improvement (IGF-I effects on hepatocytes).

Research Project

Project/Area Number 21K16342
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 54040:Metabolism and endocrinology-related
Research InstitutionKagawa University

Principal Investigator

Fukunaga Kensaku  香川大学, 医学部, 助教 (70746932)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords成人成長ホルモン分泌不全症 / 成長ホルモン / IGF-I / 脂肪肝 / ABCA1 / FoxO1 / NAFLD/NASH / IGF-1 / ソマトメジンC
Outline of Research at the Start

成長ホルモン(GH)は成人期においても代謝調節や身体的・精神機能の維持に重要である。成人GH分泌不全症(AGHD)では体脂肪・内臓脂肪の増加を認め、高TG血症、脂肪肝・非アルコール性脂肪性肝炎(NASH)を発症する。これらは最終的に肝硬変に至る予後不良な病態で、AGHD患者での臨床的重要課題である。またGHの応答ホルモンであるIGF-IもAGHDで同様に低値になるが、IGF-I補充の有効性や機序は不明である。本研究の目的はIGF-Iが肝臓での脂質代謝に及ぼすメカニズムや、AGHDの脂肪肝・NASHに対してIGF-I投与が及ぼす効果の分子メカニズムを解析し、新たな治療法を開発することである。

Outline of Final Research Achievements

Adult GH deficiency of secretion (AGHD) can lead to fatty liver to cirrhosis. The efficacy of IGF-I supplementation in this condition is unknown, and the relationship between IGF-I and ABCA1 (closely related to TG synthesis) expression was investigated in the present study, suggesting that ABCA1 expression increases upon IGF-I stimulation in HepG2 and may promote ABCA1 transcriptional activity via PI3-K/Akt/FoxO1. IGF-I treatment of hepatic lipolipidaemia in a GH-secretory-deficient mouse model increased hepatic ABCA1 expression, decreased intracellular lipid accumulation, decreased serum TG and increased HDL In FoxO1 studies, 2-ME2 promoted hepatic ABCA1 expression via the PI3K/Akt/FoxO1 pathway and decreased hepatic lipid content. . The possibility that IGF-I could be an effective therapeutic strategy for fatty liver in AGHD was demonstrated in this study through basic experiments.

Academic Significance and Societal Importance of the Research Achievements

AGHD患者に対するIGF-Iにおける意義や詳細なメカニズムは不明で、AGHDにおける脂肪肝形成のメカニズムにおけるIGF-Iの役割を明らかにし、AGHDで引き起こされる脂肪肝/NAFLD/NASHに対し、IGF-Iを補充することで脂肪肝が改善する機序の一つを解析できた学術的意義は大きい。またAGHDにおける脂肪肝改善の新規治療戦略として、IGF-IがABCA1発現促進により、脂肪肝を抑制する可能性があるという仮説を実証し、成長ホルモン分泌不全症での臨床的課題である脂肪肝に対する有効な治療戦略となる可能性について基礎実験を通して証明できた本研究成果の社会的意義は大変大きいと考えられる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (5 results)

All 2024 2023 2022

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (2 results)

  • [Journal Article] Selective Peroxisome Proliferator-Activated Receptor-α Modulator K-877 Stimulated the Expression of ABCA1 in Pancreatic Beta Cells in a Glucotoxic State2024

    • Author(s)
      Fukunaga Kensaku
    • Journal Title

      Biomedical Journal of Scientific & Technical Research

      Volume: 56 Issue: 2 Pages: 47904-47913

    • DOI

      10.26717/bjstr.2024.56.008829

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A pilot study on the effect of D-allulose on postprandial glucose levels in patients with type 2 diabetes mellitus during Ramadan fasting2022

    • Author(s)
      Japar S, Fukunaga K, Kobayashi T, Imachi H, Sato S, Saheki T, Ibata T, Yoshimura T, Soh KL, Ong SL, Muhamed Z, Murao K
    • Journal Title

      Diabetol Metab Syndr

      Volume: 14 Issue: 1 Pages: 86-91

    • DOI

      10.1186/s13098-022-00856-3

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Exendin-4 Increases Scavenger Receptor Class BI Expression via Activation of AMPK/FoxO1 in Human Vascular Endothelial Cells.2022

    • Author(s)
      Lyu J, Imachi H, Fukunaga K, Sato S, Kobayashi T, Saheki T, Japar S, Iwama H, Matsumura Y, Ozaki M, Yoshimura T, Murao K
    • Journal Title

      Curr Issues Mol Biol

      Volume: 44 Issue: 11 Pages: 5474-5484

    • DOI

      10.3390/cimb44110370

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 膵β細胞においてペマフィブラートがABCA1発現、インスリン分泌に及ぼす影響について2023

    • Author(s)
      福長健作;井上侑香;高場萌;吉村崇史;佐伯岳信;佐伯直;小林俊博;井町仁美;村尾孝児
    • Organizer
      第66回日本糖尿病学会年次学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 希少糖D-アルロースが糖代謝に与える影響と課題について2022

    • Author(s)
      福長健作
    • Organizer
      日本糖尿病学会中国四国地方会第60回総会 シンポジウム
    • Related Report
      2022 Research-status Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi