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

Elucidation of the pathophysiological role for ectopic fat accumulation in the regulation of glucose and lipid metabolism

Research Project

Project/Area Number 17K09827
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Metabolomics
Research InstitutionDepartment of Clinical Research, National Hospital Organization Kyoto Medical Center

Principal Investigator

Kusakabe Toru  独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究室長 (60452356)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords異所性脂肪蓄積 / 肥満症 / 脂肪萎縮症 / 脂肪肝 / 2型糖尿病 / サルコペニア / SGLT2阻害薬 / 低炭水化物食 / インスリン抵抗性 / インスリン分泌 / リポプロテインリパーゼ / ANGPTL8 / 脂肪膵 / レプチン / 糖尿病 / 肥満
Outline of Final Research Achievements

It has been reported that lipid accumulation in the liver, skeletal muscle, and pancreas has a profound effect on the regulation of glucose and lipid metabolism in the body, but the mechanisms in detail remain to be unknown. In this study, disease model rats for generalized lipodystrophy and obesity, seipin knockout rat and leptin knockout rat, respectively, were shown to be valid as a model for ectopic fat accumulation. Furthermore, we showed the mechanism by which nicotine promotes fatty liver to non-alcoholic steatohepatitis (NASH) using these rats. In addition, sarcopenia, that is a decrease in skeletal muscle mass and muscle strength, was observed in both rats. The mechanism of onset and progression of sarcopenia due to ectopic fat accumulation in the skeletal muscle will be elucidated in the future.

Academic Significance and Societal Importance of the Research Achievements

これまで、異所性脂肪蓄積のモデル動物として、高脂肪食摂取による食餌性肥満動物が用いられることが多かったが、肝臓や骨格筋、膵臓などの臓器に脂肪蓄積をきたすのに時間がかかる点や、餌として用いる高脂肪食(45%~60%)が実際の臨床とはかけ離れている点などが問題とされ、異所性脂肪蓄積を検討するための良いモデル動物が存在するとは言えなかった。本研究により、ヒト肥満症の病態により則した異所性脂肪蓄積モデル動物が開発されたことで、今後、肥満症におけるサルコペニアの発症・進展機序など、肥満症の病態解明がさらに進展することが期待され、学術的にも社会的にも意義がある。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (36 results)

All 2020 2019 2018 2017

All Journal Article (17 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 15 results,  Open Access: 10 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) (of which Invited: 4 results)

  • [Journal Article] Rationale, Design, and Methods of the Study of Comparison of Canagliflozin vs. Teneligliptin Against Basic Metabolic Risks in Patients with Type 2 Diabetes Mellitus (CANTABILE study): Protocol for a Randomized, Parallel-Group Comparison Trial2020

    • Author(s)
      C. Son*, Kasahara M*, Tanaka T *, Satoh-Asahara N, Kusakabe T, Nishimura K, Miyamoto Y, Kasama S, Hosoda K. *Equally contributed senior authors
    • Journal Title

      Diabetes Therapy

      Volume: 11(1) Issue: 1 Pages: 347-358

    • DOI

      10.1007/s13300-019-00717-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A combination of dietary fat intake and nicotine exposure enhances CB1 endocannabinoid receptor expression in hypothalamic nuclei in male mice2020

    • Author(s)
      Guo T*, Tanaka T*, Matsumoto M, Kaneko K, Unzai T, Ogino Y, Aotani D, Kusakabe T, Iwakura H, Miyazawa T, Sawamoto K, Minokoshi Y, Masuzaki H, Inagaki N, Nakao K. *Equally contributed senior authors
    • Journal Title

      Neuroscience Letters

      Volume: 714 Pages: 13455-13455

    • DOI

      10.1016/j.neulet.2019.134550

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Seipin-linked congenital generalized lipodystrophy type 2: a rare case with multiple lytic and pseudo-osteopoikilosis lesions.2019

    • Author(s)
      Yamamoto A, Kusakabe T, Sato K, Tokizaki T, Sakurai K, Abe S.
    • Journal Title

      Acta Radiol Open.

      Volume: 12 Issue: 12 Pages: 11-8

    • DOI

      10.1177/2058460119892407

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Background characteristics and postoperative outcomes of insufficient weight loss after laparoscopic sleeve gastrectomy in Japanese patients.2019

    • Author(s)
      Saiki A, Yamaguchi T, Tanaka S, Sasaki A, Naitoh T, Seto Y, Matsubara H, Yokote K, Okazumi S, Ugi S, Yamamoto H, Ohta M, Ishigaki Y, et al
    • Journal Title

      Ann Gastroenterol Surg.

      Volume: 3 Issue: 6 Pages: 638-647

    • DOI

      10.1002/ags3.12285

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical characteristics in two patients with partial lipodystrophy and Type A insulin resistance syndrome due to a novel heterozygous missense mutation in the insulin receptor gene.2019

    • Author(s)
      Iwanishi M, Kusakabe T, Azuma C, Tezuka Y, Yamamoto Y, Ito-Kobayashi J, Washiyama M, Morimoto M, Ebihara K.
    • Journal Title

      Diabetes Res Clin Pract.

      Volume: 152 Pages: 79-87

    • DOI

      10.1016/j.diabres.2019.04.034

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of dapagliflozin on the serum levels of fibroblast growth factor?21 and myokines and muscle mass in Japanese patients with type?2 diabetes: A randomized, controlled trial2019

    • Author(s)
      Yamakage Hajime、Tanaka Masashi、Inoue Takayuki、Odori Shinji、Kusakabe Toru、Satoh‐Asahara Noriko
    • Journal Title

      Journal of Diabetes Investigation

      Volume: none Issue: 3 Pages: 653-661

    • DOI

      10.1111/jdi.13179

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 肥満、糖尿病に合併するサルコペニア2019

    • Author(s)
      日下部 徹
    • Journal Title

      BIO Clinica

      Volume: 8 Pages: 78-82

    • Related Report
      2019 Annual Research Report
  • [Journal Article] AGPAT2遺伝子変異による先天性全身性脂肪萎縮症の臨床的特徴2019

    • Author(s)
      日下部徹、海老原健、中尾一和
    • Journal Title

      The Lipid

      Volume: 30 Pages: 98-102

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Clinical Characteristics, Phenotype of Lipodystrophy and a Genetic Analysis of Six Diabetic Japanese Women with Familial Partial Lipodystrophy in a Diabetic Outpatient Clinic2018

    • Author(s)
      Iwanishi M, Ito-Kobayashi J, Washiyama M, Kusakabe T, Ebihara K.
    • Journal Title

      Internal Medicine

      Volume: 57 Issue: 16 Pages: 2301-2313

    • DOI

      10.2169/internalmedicine.0225-17

    • NAID

      130007434990

    • ISSN
      0918-2918, 1349-7235
    • Year and Date
      2018-08-15
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] A potential novel pathological implication of serum soluble triggering receptor expressed on myeloid cell 2 in insulin resistance in a general Japanese population: The Hisayama study2018

    • Author(s)
      Tanaka Masashi、Honda Takanori、Yamakage Hajime、Hata Jun、Yoshida Daigo、Hirakawa Yoichiro、Shibata Mao、Inoue Takayuki、Kusakabe Toru、Satoh-Asahara Noriko、Ninomiya Toshiharu
    • Journal Title

      Diabetes Research and Clinical Practice

      Volume: 146 Pages: 225-232

    • DOI

      10.1016/j.diabres.2018.10.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats2018

    • Author(s)
      Izumi Ryota、Kusakabe Toru、Noguchi Michio、Iwakura Hiroshi、Tanaka Tomohiro、Miyazawa Takashi、Aotani Daisuke、Hosoda Kiminori、Kangawa Kenji、Nakao Kazuwa
    • Journal Title

      Journal of Lipid Research

      Volume: 59 Issue: 9 Pages: 1575-1585

    • DOI

      10.1194/jlr.m082099

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Role of serum myostatin in the association between hyperinsulinemia and muscle atrophy in Japanese obese patients.2018

    • Author(s)
      Tanaka M, Masuda S, Yamakage H, Inoue T, Ohue-Kitano R, Yokota S, Kusakabe T, Wada H, Sanada K, Ishii K, Hasegawa K, Shimatsu A, Satoh-Asahara N.
    • Journal Title

      Diabetes Res Clin Pract.

      Volume: 142 Pages: 195-202

    • DOI

      10.1016/j.diabres.2018.05.041

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] α-Linolenic acid?derived metabolites from gut lactic acid bacteria induce differentiation of anti-inflammatory M2 macrophages through G protein-coupled receptor 402018

    • Author(s)
      Ohue-Kitano Ryuji、Iwase Mari、Tanaka Masashi、Masuda Shinya、Inoue Takayuki、Yamakage Hajime、Kusakabe Toru、Tani Fumito、Shimatsu Akira、Takahashi Nobuyuki、Ogawa Jun、Satoh-Asahara Noriko、Kawada Teruo
    • Journal Title

      The FASEB Journal

      Volume: 32 Issue: 1 Pages: 304-318

    • DOI

      10.1096/fj.201700273r

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chemokine (C-X-C motif) ligand 1 is a myokine induced by palmitate and is required for myogenesis in mouse satellite cells2017

    • Author(s)
      Masuda S.、Tanaka M.、Inoue T.、Ohue-Kitano R.、Yamakage H.、Muranaka K.、Kusakabe T.、Shimatsu A.、Hasegawa K.、Satoh-Asahara N.
    • Journal Title

      Acta Physiologica

      Volume: 222 Issue: 3

    • DOI

      10.1111/apha.12975

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of functional profiles of gut microbiota from 16S rRNA metagenomic data provides a more robust evaluation of gut dysbiosis occurring in Japanese type 2 diabetic patients2017

    • Author(s)
      Inoue R, Ohue-Kitano R, Tsukahara T, Tanaka M, Masuda S, Inoue T, Yamakage H, Kusakabe T, Hasegawa K, Shimatsu A, Satoh-Asahara N
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 61 Issue: 3 Pages: 217-221

    • DOI

      10.3164/jcbn.17-44

    • NAID

      130006191913

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum soluble TREM2 is a potential novel biomarker of cognitive impairment in Japanese non-obese patients with diabetes2017

    • Author(s)
      Tanaka M.、Yamakage H.、Masuda S.、Inoue T.、Ohue-Kitano R.、Araki R.、Matoba Y.、Saito M.、Nagaoka T.、Yonezawa K.、Tanaka T.、Suzuki M.、Sawamura M.、Nishimura M.、Odori S.、Wada H.、Kotani K.、Kusakabe T.、Shimatsu A.、Hasegawa K.、Satoh-Asahara N.
    • Journal Title

      Diabetes & Metabolism

      Volume: ー Issue: 1 Pages: 30470-30476

    • DOI

      10.1016/j.diabet.2017.06.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Omega-3 polyunsaturated fatty acids suppress the inflammatory responses of lipopolysaccharide-stimulated mouse microglia by activating SIRT1 pathways.2017

    • Author(s)
      Inoue T, Tanaka M, Masuda S, Ohue-Kitano R, Yamakage H, Muranaka K, Wada H, Kusakabe T, Shimatsu A, Hasegawa K, Satoh-Asahara N
    • Journal Title

      Biochim Biophys Acta

      Volume: 1862 Issue: 5 Pages: 552-560

    • DOI

      10.1016/j.bbalip.2017.02.010

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 肥満糖尿病モデル動物において低炭水化物食とSGLT2阻害薬が体組成および糖脂質代謝に及ぼす影響2019

    • Author(s)
      日下部徹、横田繁史、清水美佳、井上隆之、田中将志、北野隆司、山陰一、浅原哲子
    • Organizer
      第40回日本肥満学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肥満症や2型糖尿病治療における低炭水化物食とSGLT2阻害薬の有用性の相違2019

    • Author(s)
      日下部徹、井上隆之、田中将志、山陰一、浅原哲子
    • Organizer
      第21回応用薬理シンポジウム
    • Related Report
      2019 Annual Research Report
  • [Presentation] 四肢優位の特異な脂肪沈着を契機に紹介され、脂肪性浮腫と診断した肥満症の一例2019

    • Author(s)
      野村英生、日下部徹、小鳥真司、浅原哲子
    • Organizer
      第92回日本内分泌学会学術総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 女性の肥満と痩せにおけるサルコペニアの実態2019

    • Author(s)
      日下部徹、浅原哲子
    • Organizer
      第40回日本肥満学会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 国立病院機構ネットワーク共同研究による2型糖尿病とサルコペニア2019

    • Author(s)
      日下部徹、浅原哲子
    • Organizer
      第74回日本体力医学会大会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] これからの糖尿病治療戦略について2018

    • Author(s)
      日下部徹
    • Organizer
      近畿国立病院薬剤師会学術講演会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 肥満症・糖尿病におけるサルコペニア進展機序の解明2018

    • Author(s)
      日下部徹、浅原哲子
    • Organizer
      第39回日本肥満学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] AGPAT2遺伝子変異による先天性全身性脂肪萎縮症の臨床的特徴2018

    • Author(s)
      日下部徹、青谷大介、阿部恵、冨田努、海老原健、中尾一和
    • Organizer
      第61回日本糖尿病学会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肥満患者における骨格筋由来液性因子・マイオスタチンを介した耐糖能悪化と骨格筋萎縮2018

    • Author(s)
      田中将志、増田慎也、山陰一、井上隆之、北野隆司、横田繁史、村中和哉、日下部徹、和田啓道、真田樹義、石井好二郎、長谷川浩二、島津章、浅原哲子
    • Organizer
      第61回日本糖尿病学会
    • Related Report
      2018 Research-status Report
  • [Presentation] ANGPTL8は肥満に合併する高中性脂肪血症発症に関与する可能性がある2018

    • Author(s)
      日下部徹、泉諒太、野口倫生、岩倉浩、田中智洋、青谷大介、細田公則、寒川賢治、中尾一和
    • Organizer
      第91回日本内分泌学会学術総会
    • Related Report
      2018 Research-status Report
  • [Presentation] 肥満症患者における心血管疾患発症リスク因子としての高尿酸血症―多施設共同前向き研究―2017

    • Author(s)
      日下部徹、山陰一、村中和哉、小谷和彦、山田努、荒木里香、岡嶋泰一郎、大石まり子、島津章、浅原哲子
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肥満患者の糖代謝能・骨格筋量制御における筋肉由来液状因子・myostatinの病態意義2017

    • Author(s)
      横田繁史、増田慎也、田中将志、山陰一、村中和哉、井上隆之、北野隆司、真田樹義、石井好二郎、日下部徹、島津章、浅原哲子
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Research-status Report
  • [Presentation] ANGPTL8ノックアウトラットの開発と肥満症治療標的としてのANGPTL8の意義の解明2017

    • Author(s)
      泉諒太、日下部徹、野口倫生、岩倉浩、小山博之、坂東美佳、宮澤崇、田中智洋、寒川賢治、中尾一和
    • Organizer
      第38回日本肥満学会
    • Related Report
      2017 Research-status Report
  • [Presentation] サルコペニア肥満の効果的診断法の開発2017

    • Author(s)
      日下部徹、横田繁史、田中将志、増田慎也、井上隆之、北野隆司、山陰一、村中和哉、石井好二郎、真田樹義、浅原哲子
    • Organizer
      第36回日本臨床運動療法学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] 白血球減少を呈した脂肪萎縮症の1例2017

    • Author(s)
      井上真由美、冨田努、森栄作、大野洋一、小野雅仁、八十田明宏、稲垣暢也、北野俊行、日下部徹、中尾一和
    • Organizer
      日本内科学会近畿支部主催 第208回近畿地方会
    • Related Report
      2017 Research-status Report
  • [Presentation] ANGPTL8のノックアウトラット開発とその糖・脂質代謝調節における意義の検討2017

    • Author(s)
      泉諒太、日下部徹、野口倫生、岩倉浩、小山博之、坂東美佳、宮澤崇、田中智洋、寒 川賢治、中尾一和
    • Organizer
      第60回日本糖尿病学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 肥満症患者における心血管疾患発症リスク因子としての高尿酸血症―多施設共同前向き肥満症コホート―2017

    • Author(s)
      日下部徹、山陰一、小谷和彦、山田努、荒木里香、岡嶋泰一郎、大石まり子、島津章、浅原哲子
    • Organizer
      第60回日本糖尿病学会
    • Related Report
      2017 Research-status Report
  • [Presentation] CAVIは肥満症患者の心血管疾患発症予測マーカーとなる―多施設共同前向き肥満症コホート―2017

    • Author(s)
      山陰一、日下部徹、小谷和彦、山田努、荒木里香、岡嶋泰一郎、大石まり子
    • Organizer
      第60回日本糖尿病学会
    • Related Report
      2017 Research-status Report
  • [Presentation] メタボリックシンドローム症例におけるANGPTL8/Betatrophinの組織別遺伝子発現の検討2017

    • Author(s)
      日下部徹、泉諒太、野口倫生、宮澤崇、田中智洋、寒川賢治、中尾一和
    • Organizer
      第90回日本内分泌学会学術総会
    • Related Report
      2017 Research-status Report

URL: 

Published: 2017-04-28   Modified: 2021-02-19  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi