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遺伝学と生理学の融合によるヒト寒冷適応進化の実証研究

Research Project

Project/Area Number 18H02515
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 45050:Physical anthropology-related
Research InstitutionThe University of Tokyo

Principal Investigator

中山 一大  東京大学, 大学院新領域創成科学研究科, 准教授 (90433581)

Co-Investigator(Kenkyū-buntansha) 岩本 禎彦  自治医科大学, 医学部, 教授 (10232711)
斉藤 昌之  北海道大学, 獣医学研究院, 名誉教授 (80036441)
西村 貴孝  九州大学, 芸術工学研究院, 講師 (80713148)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
Keywords褐色脂肪細胞 / 熱産生 / ゲノム多様性 / 寒冷適応 / ヒト / ゲノム / 褐色脂肪組織 / SNP / 遺伝学 / 生理学 / 一塩基多型 / 進化
Outline of Annual Research Achievements

ヒトの寒冷適応能力の多様化の分子基盤を、遺伝学と生理学の手法を融合させて解明することを目的とした本課題では、関東在住の日本人・中国人50名を対象として、サーマルカメラを用いた褐色脂肪組織活性の測定実験を実施した。被検者に薄着で19℃に保温した測定室に滞在してもらい、その間、褐色脂肪組織の代表的な局在部位である鎖骨上窩部と、コントロール部位である胸部の温度変化をサーマルカメラで計測することにより、寒冷刺激時の褐色脂肪組織活性を測定した。同時に、ゲノム抽出のための唾液試料の提供を受けた。この50名の加えて、前年度から収集を続けてきた北海道在住の日本人成人の褐色脂肪組織活性情報付き(PET-CT法で測定)のゲノムDNA試料406検体分を用いて、前年度までの研究で同定されてきたいくつかの候補ゲノム多型について、褐色脂肪組織活性の個人差への寄与を調査した。その結果、褐色脂肪組織・白色脂肪組織での代謝調整に関与していることが報告され、肥満や2型糖尿病を始め各種代謝異常症との関連が繰り返して指摘されてきたある遺伝子の多型が褐色脂肪の活性と関連していることが、2つの独立コホートの解析で明らかになった。さらに、九州在住の成人を対象とした人工気候室での寒冷曝露実験では、この多型が被検者の酸素消費量や深部体温の変化とも関連していることが証明された。この遺伝子の多型は、肥満や2型糖尿病以外にも、血圧、免疫機能、呼吸機能などの多様性にも関連していることが報告されており、熱産生機能の多様化が、寒冷適応能以外の様々な身体機能と深く連関していることを示唆する結果となった。

Research Progress Status

令和2年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和2年度が最終年度であるため、記入しない。

Report

(3 results)
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report

Research Products

(31 results)

All 2022 2021 2020 2019 2018

All Journal Article (15 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 15 results,  Open Access: 14 results) Presentation (16 results) (of which Int'l Joint Research: 8 results,  Invited: 5 results)

  • [Journal Article] ILDR2 stabilization is regulated by its interaction with GRP782021

    • Author(s)
      Watanabe Kazuhisa、Nakayama Kazuhiro、Ohta Satoshi、Matsumoto Ayumi、Tsuda Hidetoshi、Iwamoto Sadahiko
    • Journal Title

      Sci Rep.

      Volume: 11 Pages: 8414-8414

    • DOI

      10.1038/s41598-021-87884-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 遺伝子対応栄養指導を用いた閉経後女性の肥満度および骨密度の変化.2021

    • Author(s)
      不老美也子・蒲池桂子・田中明・吉澤剛士・中山一大・香川靖雄
    • Journal Title

      日本病態栄養学会誌

      Volume: 24 Pages: 161-172

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Associations of erythrocyte fatty acid compositions with FADS1 gene polymorphism in Japanese mothers and infants.2020

    • Author(s)
      Nita R, Kawabata T, Kagawa Y, Nakayama K, Yanagisawa Y, Iwamoto S, Kimura F, Miyazawa T, Tatsuta N, Arima T, Yaegashi N, Nakai K.
    • Journal Title

      Prostaglandins Leukot Essent Fatty Acids.

      Volume: 152 Pages: 102031-102031

    • DOI

      10.1016/j.plefa.2019.102031

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kbtbd11 contributes to adipocyte homeostasis through the activation of upstream stimulatory factor 1.2019

    • Author(s)
      Watanabe K, Yokota K, Yoshida K, Matsumoto A, Iwamoto S
    • Journal Title

      Heliyon

      Volume: 5

    • DOI

      10.1016/j.heliyon.2019.e02777

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel upstream transcription factor 1 target gene N4bp2l1 that regulates adipogenesis.2019

    • Author(s)
      Watanabe K, Yokota K, Yoshida K, Matsumoto A, Iwamoto S
    • Journal Title

      Biochem Biophys Rep.

      Volume: 20 Pages: 100676-100676

    • DOI

      10.1016/j.bbrep.2019.100676

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Kbtbd11 gene expression in adipose tissue increases in response to feeding and affects adipocyte differentiation2019

    • Author(s)
      Watanabe Kazuhisa、Yoshida Ken、Iwamoto Sadahiko
    • Journal Title

      J Diabetes Investig.

      Volume: 印刷中 Pages: 925-932

    • DOI

      10.1111/jdi.12995

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Applicability of Supraclavicular Oxygenated and Total Hemoglobin Evaluated by Near-Infrared Time-Resolved Spectroscopy as Indicators of Brown Adipose Tissue Density in Humans2019

    • Author(s)
      Nirengi Shinsuke、Fuse Sayuri、Amagasa Shiho、Homma Toshiyuki、Kime Ryotaro、Kuroiwa Miyuki、Endo Tasuki、Sakane Naoki、Matsushita Mami、Saito Masayuki、Kurosawa Yuko、Hamaoka Takafumi
    • Journal Title

      Int J Mol Sci

      Volume: 20 Pages: 2214-2214

    • DOI

      10.3390/ijms20092214

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of circulating exosomal miR-122 levels with BAT activity in healthy humans2019

    • Author(s)
      Okamatsu-Ogura Yuko、Matsushita Mami、Bariuan Jussiaea Valente、Nagaya Kazuki、Tsubota Ayumi、Saito Masayuki
    • Journal Title

      Scietific Reports

      Volume: 9 Pages: 13243-13243

    • DOI

      10.1038/s41598-019-49754-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] BCAA catabolism in brown fat controls energy homeostasis through SLC25A442019

    • Author(s)
      Yoneshiro T, Wang Q, Tajima K, Matsushita M, Maki H, Igarashi K, Dai Z, White P J, McGarrah R W, Ilkayeva O R, Deleye Y, Oguri Y, Kuroda M, Ikeda K, Li H, Ueno A, Ohishi M, Ishikawa T, Kim K, Chen Y, Sponton C H, Pradhan R N, Majd H, Greiner V J, Yoneshiro M, Brown Z, Chondronikola M, Takahashi H, Goto T, et al
    • Journal Title

      Nature

      Volume: 572 Pages: 614-619

    • DOI

      10.1038/s41586-019-1503-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetic variants influencing obesity-related traits in Japanese population.2019

    • Author(s)
      Nakayama K, Inaba Y
    • Journal Title

      Ann Hum Biol .

      Volume: 46 Pages: 298-304

    • DOI

      10.1080/03014460.2019.1644373

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] THE RELATIONSHIP BETWEEN HUMAN COLD ADAPTATION AND UCP1 GENOTYPE.2019

    • Author(s)
      西村 貴孝
    • Journal Title

      Japanese Journal of Physiological Anthropology

      Volume: 24 Issue: 2 Pages: 81-85

    • DOI

      10.20718/jjpa.24.2_81

    • NAID

      130007677030

    • ISSN
      1342-3215, 2432-0986
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Translational Aspects of Brown Fat Activation by Food-Derived Stimulants2019

    • Author(s)
      Yoneshiro Takeshi、Matsushita Mami、Saito Masayuki
    • Journal Title

      Handbook of Experimental Pharmacology

      Volume: 251 Pages: 11-19

    • DOI

      10.1007/164_2018_159

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GENETICS AND ADAPTATION2018

    • Author(s)
      中山一大
    • Journal Title

      Japanese Journal of Physiological Anthropology

      Volume: 23 Issue: 4 Pages: 189-191

    • DOI

      10.20718/jjpa.23.4_189

    • NAID

      130007580267

    • ISSN
      1342-3215, 2432-0986
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Brown adipose tissue density measured by near-infrared time-resolved spectroscopy in Japanese, across a wide age range2018

    • Author(s)
      Fuse Sayuri、Nirengi Shinsuke、Amagasa Shiho、Homma Toshiyuki、Kime Ryotaro、Endo Tasuki、Sakane Naoki、Matsushita Mami、Saito Masayuki、Yoneshiro Takeshi、Kurosawa Yuko、Hamaoka Takafumi
    • Journal Title

      J Biomed Opt.

      Volume: 23 Pages: 065002-065002

    • DOI

      10.1117/1.jbo.23.6.065002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ADAPTATION TO THERMAL ENVIRONMENT – LIFESTYLE MODIFICATION AFFECTING HUMAN ADAPTABILITY TO THERMAL ENVIRONMENT –2018

    • Author(s)
      若林 斉、前田 享史、西村 貴孝
    • Journal Title

      Japanese Journal of Physiological Anthropology

      Volume: 23 Issue: 4 Pages: 167-170

    • DOI

      10.20718/jjpa.23.4_167

    • NAID

      130007580264

    • ISSN
      1342-3215, 2432-0986
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒトの環境適応と生活習慣病.2022

    • Author(s)
      中山一大
    • Organizer
      第15回日本がん検診・診断学会習熟講習会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Recent advances in understanding human genetic adaptation to cold environments.2021

    • Author(s)
      Nakayma K
    • Organizer
      The 2nd AsiaEvo Conference
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 病気へのかかりやすさと環境適応.2021

    • Author(s)
      中山一大
    • Organizer
      第75回日本人類学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 牧畜民における食への遺伝的適応.2021

    • Author(s)
      中山一大
    • Organizer
      第75回日本人類学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Diversity in genetic susceptibility of myopia in Europeans.2021

    • Author(s)
      Xia Tiang・中山一大
    • Organizer
      第75回日本人類学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] モンゴル人の脂質異常症抵抗性は遺伝的か?Polygenic risk score を用いた検証.2021

    • Author(s)
      胡琦・岩本禎彦・中山一大
    • Organizer
      第82回日本生理人類学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Changes In Blood Component And DNA Methylation Patterns In Healthy Men Exposed Hypobaric Hypoxia2019

    • Author(s)
      Motoi M, Toyoshima H, Nakayama K, Kishida F, Shin S, Nishimura T, Yasukouchi Y, Katsumura T, Oota H, Maeda T, Watanuki S
    • Organizer
      The 14th International Congress of Physiological Anthropology.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] "Individual and sex differences of percutaneous arterial oxygen saturation (SpO2) in Bolivian people "2019

    • Author(s)
      Nishimura T, Ohnishi M, Nishihara M, Ugarute J, Yasukochi Y, Fukuda H, Watanuki S, Aoyagi K
    • Organizer
      The 14th International Congress of Physiological Anthropology.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Genome wide scanning for loci influencing brown adipose tissue activity in Japanese adults.2019

    • Author(s)
      Nakayama K
    • Organizer
      The 14th International Congress of Physiological Anthropology.
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Local Adaptation and Susceptibility to Lifestyle-related Diseases in East Asia.2019

    • Author(s)
      Nakayama K
    • Organizer
      Crossing Boundaries
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Detecting signatures of polygenic selection in East Asians2018

    • Author(s)
      Kazuhiro Nakayama
    • Organizer
      SMBE2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒトの表現型とエピゲノムの多様性2018

    • Author(s)
      中山一大
    • Organizer
      第41回日本分子生物学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ヒトの寒冷適応とUCP1遺伝子多型との関連2018

    • Author(s)
      西村 貴孝
    • Organizer
      日本生理人類学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Human cold adaptation and importance of UCP1 genotype to non-shivering thermogenesis2018

    • Author(s)
      Takayuki Nishimura
    • Organizer
      Physiological Anthropology and Human Ecology: Studies in Modern and Ancient Populations
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Study on multiple organs coordination for non-shivering thermogenesis and vasomotor control in mild cold environment in human2018

    • Author(s)
      Kentaro Matsumoto, Yusuke Kobori, Hitoshi Wakabayashi, Mami Matsushita, Toshimitsu Kameya, Takafumi Maeda, Masayuki Saito
    • Organizer
      7th International Conference on the Physiology and Pharmacology of Temperature Regulation
    • Related Report
      2018 Annual Research Report
  • [Presentation] Supraclavicular tissue total hemoglobin determined by near-infrared time-resolved spectroscopy as indicators of brown adipose tissue characteristics in humans2018

    • Author(s)
      Takafumi Hamaoka, Shinsuke Nirengi, Sayuri Fuse, Shiho Amagasa, Toshiyuki Homma, Ryotaro Kime, Miyuki Kuroiwa, Tasuki Endo, Naoki Sakane, Mami Matsushita, Masayuki Saito, Takeshi Yoneshiro, Yuko Kurosawa
    • Organizer
      International Symposium: Role of Brown Adipose Tissue in Human Health
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2018-04-23   Modified: 2022-12-28  

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