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Genetic basis for the variation of thermogensis in humanss

Research Project

Project/Area Number 21H02571
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

Nakayama Kazuhiro  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) 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, 准教授 (80713148)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2022: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywords熱産生 / 褐色脂肪組織 / ヒト / 寒冷適応 / 飢餓適応 / ゲノム多型 / ヒトゲノム多様性 / 熱産生能力 / 東アジア人 / 環境適応 / ゲノム / 進化
Outline of Research at the Start

ヒトは、高緯度地域に進出した際に低温環境への遺伝的適応を果たしたと考えられている。この遺伝的適応には褐色脂肪組織が関与していたことが支持されている。さらに、褐色脂肪組織による熱産生は、感染症、飢餓、社会ストレス等への適応現象にも寄与していることも明らかになっており、ヒトの熱産生能力の多様化が、寒冷適応のみならず、拡散に伴う社会構造の変化等とも密接に関わっている可能性が浮上してきた。東アジア人を対象とした全ゲノム規模の多型情報による進化遺伝学解析とヒト個体を対象とした詳細な生理実験、そして遺伝型-表現型関連解析を通して、ヒトの熱産生能力の多様化に遺伝的適応が関与した証拠を発見する。

Outline of Final Research Achievements

The human body has the ability to convert energy into heat. This function is closely related to the response to various stresses, such as changes in external temperature, infection, and starvation. Furthermore, it is becoming clear that there are large individual and group differences in human heat production capacity. With the ultimate goal of clarifying the evolutionary background of individual differences in human heat production capacity, this project attempted to identify genomic regions involved in individual differences in the activity of brown adipose tissue, a representative heat-producing organ, and collected genomic samples from adults whose brown adipose tissue activity was measured using multiple methods. From a series of analyses using these samples, we succeeded in identifying a novel gene locus involved in heat-producing diversity, ahead of any other researchers in the world.

Academic Significance and Societal Importance of the Research Achievements

本課題では、これまで謎に包まれていた褐色脂肪組織活性の個人差に寄与する遺伝子の一部が明らかにすることに成功した。さらにこれらの遺伝子の進化パターン等の解析から、ヒトの進化において寒冷、飢餓、感染症等のストレスへの多面的な適応が共通の熱産生遺伝子によって制御されている可能性が明るみなった。褐色脂肪組織による熱産生は、全身のエネルギー代謝を亢進することで肥満や2型糖尿病に抵抗的にはたらくことが期待されている。したがって、これらの成果は、ヒトの適応進化史の解明のみならず、各種生活習慣病の新たな予防・治療戦略の創出にも寄与できるだろう。

Report

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

    (28 results)

All 2024 2023 2022 2021

All Journal Article (13 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 13 results,  Open Access: 13 results) Presentation (15 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results)

  • [Journal Article] Genetic evidence for involvement of β2-adrenergic receptor in brown adipose tissue thermogenesis in humans2024

    • Author(s)
      Ishida Yuka、Matsushita Mami、Yoneshiro Takeshi、Saito Masayuki、Fuse Sayuri、Hamaoka Takafumi、Kuroiwa Miyuki、Tanaka Riki、Kurosawa Yuko、Nishimura Takayuki、Motoi Midori、Maeda Takafumi、Nakayama Kazuhiro
    • Journal Title

      International Journal of Obesity

      Volume: - Issue: 8 Pages: 1110-1117

    • DOI

      10.1038/s41366-024-01522-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mevalonate biosynthesis pathway regulates the development and survival of brown adipocytes2023

    • Author(s)
      Kwon Jungin、Yeh Yu-Sheng、Kawarasaki Satoko、Minamino Hiroto、Fujita Yoshihito、Okamatsu-Ogura Yuko、Takahashi Haruya、Nomura Wataru、Matsumura Shigenobu、Yu Rina、Kimura Kazuhiro、Saito Masayuki、Inagaki Nobuya、Inoue Kazuo、Kawada Teruo、Goto Tsuyoshi
    • Journal Title

      iScience

      Volume: 26 Issue: 3 Pages: 106161-106161

    • DOI

      10.1016/j.isci.2023.106161

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Thermogenic Brown Fat in Humans: Implications in Energy Homeostasis, Obesity and Metabolic Disorders2023

    • Author(s)
      Saito Masayuki、Okamatsu-Ogura Yuko
    • Journal Title

      The World Journal of Men's Health

      Volume: 41 Issue: 3 Pages: 489-507

    • DOI

      10.5534/wjmh.220224

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endocrine, inflammatory and immune responses and individual differences in acute hypobaric hypoxia in lowlanders2023

    • Author(s)
      Nishimura Takayuki、Motoi Midori、Toyoshima Hideo、Kishida Fumi、Shin Sora、Katsumura Takafumi、Nakayama Kazuhiro、Oota Hiroki、Higuchi Shigekazu、Watanuki Shigeki、Maeda Takafumi
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 12659-12659

    • DOI

      10.1038/s41598-023-39894-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Signatures of adaptation in myopia-related genes on the sunlight exposure hypothesis2023

    • Author(s)
      Xia Tian、Nakayama Kazuhiro
    • Journal Title

      Journal of Physiological Anthropology

      Volume: 42 Issue: 1 Pages: 25-25

    • DOI

      10.1186/s40101-023-00341-4

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Investigation of Maternal Diet and FADS1 Polymorphism Associated with Long-Chain Polyunsaturated Fatty Acid Compositions in Human Milk2022

    • Author(s)
      Niwa Sakurako、Kawabata Terue、Shoji Kumiko、Ogata Hiromitsu、Kagawa Yasuo、Nakayama Kazuhiro、Yanagisawa Yoshiko、Iwamoto Sadahiko、Tatsuta Nozomi、Asato Kaname、Arima Takahiro、Yaegashi Nobuo、Nakai Kunihiko
    • Journal Title

      Nutrients

      Volume: 14 Issue: 10 Pages: 2160-2160

    • DOI

      10.3390/nu14102160

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genome-wide DNA methylation status of Mongolians exhibits signs of cellular stress response related to their nomadic lifestyle2022

    • Author(s)
      Inaba Yuta、Iwamoto Sadahiko、Nakayama Kazuhiro
    • Journal Title

      Journal of Physiological Anthropology

      Volume: 41 Issue: 1 Pages: 30-30

    • DOI

      10.1186/s40101-022-00305-0

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Selenoprotein P-mediated reductive stress impairs cold-induced thermogenesis in brown fat2022

    • Author(s)
      Oo Swe Mar、Oo Hein Ko、Takayama Hiroaki、Ishii Kiyo-aki、Takeshita Yumie、Goto Hisanori、Nakano Yujiro、Kohno Susumu、Takahashi Chiaki、Nakamura Hiroyuki、Saito Yoshiro、Matsushita Mami、Okamatsu-Ogura Yuko、Saito Masayuki、Takamura Toshinari
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 13 Pages: 110566-110566

    • DOI

      10.1016/j.celrep.2022.110566

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Brown adipose tissue-associated postprandial thermogenesis in humans: Different effects of isocaloric meals rich in carbohydrate, fat, and protein2022

    • Author(s)
      Aita S, Matsushita M*, Yoneshiro T, Hatano T, Kameya T, Ohkubo I, Saito M
    • Journal Title

      Front Endocrinol

      Volume: 9 Pages: 1040444-1040444

    • DOI

      10.3389/fnut.2022.1040444

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Individual variations and sex differences in hemodynamics and percutaneous arterial oxygen saturation (SpO2) in Tibetan highlanders of Tsarang in the Mustang district of Nepal2022

    • Author(s)
      Nishimura Takayuki、Arima Hiroaki、Koirala Sweta、Ito Hiromu、Yamamoto Taro
    • Journal Title

      Journal of Physiological Anthropology

      Volume: 41 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s40101-022-00282-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prolonged Treatment with Grains of Paradise (<i>Aframomum melegueta</i>) Extract Recruits Adaptive Thermogenesis and Reduces Body Fat in Humans with Low Brown Fat Activity2021

    • Author(s)
      YONESHIRO Takeshi、MATSUSHITA Mami、SUGITA Jun、AITA Sayuri、KAMEYA Toshimitsu、SUGIE Hiroki、SAITO Masayuki
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 67 Issue: 2 Pages: 99-104

    • DOI

      10.3177/jnsv.67.99

    • NAID

      130008031493

    • ISSN
      0301-4800, 1881-7742
    • Year and Date
      2021-04-30
    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [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

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 8414-8414

    • DOI

      10.1038/s41598-021-87884-7

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Diurnal variations of brown fat thermogenesis and fat oxidation in humans2021

    • Author(s)
      Matsushita Mami、Nirengi Shinsuke、Hibi Masanobu、Wakabayashi Hitoshi、Lee Sang-il、Domichi Masayuki、Sakane Naoki、Saito Masayuki
    • Journal Title

      International Journal of Obesity

      Volume: 45 Issue: 11 Pages: 2499-2505

    • DOI

      10.1038/s41366-021-00927-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 寒冷地域で自然選択を受けた遺伝子多型の褐色脂肪組織活性への影響の検証2023

    • Author(s)
      石田悠華、松下真美、米代武司、斉藤昌之、中山一大
    • Organizer
      第44回日本肥満学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Decomposing polygenic adaptation of myopia on the sunlight exposure hypothesis2023

    • Author(s)
      Tian Xia, Kazuhiro Nakayama
    • Organizer
      75th Annual Meeting of American Society of Human Genetics
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] β2-AR、β3-ARおよびUCP1遺伝子多型がヒトの褐色脂肪組織活性に及ぼす影響2023

    • Author(s)
      石田悠華、松下真美、米代武司、斉藤昌之 、布施沙由理、浜岡隆文、西村貴孝、本井碧、前田享史、中山一 大
    • Organizer
      第43回日本肥満学会 第40回日本肥満症治療学会学術集会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 褐色脂肪組織活性を指標とした寒冷適応候補遺伝子多型の機能評価2023

    • Author(s)
      石田悠華、松下真美、米代武司、斉藤昌之、中山一大
    • Organizer
      第77回日本人類学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] The adaptive origins of the genetic basis of nearsightedness2023

    • Author(s)
      Tian Xia, Kazuhiro Nakayama
    • Organizer
      第77回日本人類学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Are genes under positive selection in high latitudes associated with brown adipose tissue activity in East Asians and contributing to cold adaptation?2023

    • Author(s)
      Yuka Ishida, Mami Matsushita, Takeshi Yoneshiro, Masayuki Saito, Kazuhiro Nakayama
    • Organizer
      16th International Congress of Physiological Anthropology
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 褐色脂肪組織活性の多様性に関与する遺伝子多型の探索 ―東アジア人の寒冷適応進化の解明に向けて―2023

    • Author(s)
      石田悠華
    • Organizer
      日本生理人類学会大会第84回大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 熱産生能力の遺伝的多様性と寒冷適応2023

    • Author(s)
      中山一大
    • Organizer
      第77回日本人類学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] ヒトの褐脂肪組織活性と体温の維持にはADRB2遺伝子が関与する2022

    • Author(s)
      石田悠華、松下真美、米代武司、斉藤昌之、布施沙由理、浜岡隆文、西村貴孝、本井碧、前田享史、中山一大
    • Organizer
      第76回日本人類学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Detection of adaptation to light environment in myopia-associated loci in humans2022

    • Author(s)
      Tian Xia, Kazuhiro Nakayama
    • Organizer
      第76回日本人類学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] β2-AR、β3-AR およびUCP1 遺伝子多型がヒトの褐色脂肪組織活性に 及ぼす影響2022

    • Author(s)
      石田悠華、松下真美、米代武司、斉藤昌之、布施沙由理、浜岡隆文、西村貴孝、本井碧、前田享史、中山一大
    • Organizer
      第43回日本肥満学会
    • Related Report
      2022 Annual Research Report
  • [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
      2021 Annual Research Report
    • Invited
  • [Presentation] Recent advances in understanding human genetic adaptation to cold environments.2021

    • Author(s)
      Nakayama K
    • Organizer
      The 2nd Asia-Evo Conference
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [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
      2021 Annual Research Report
  • [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
      2021 Annual Research Report
    • Invited

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

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