Establishment of a novel research strategy for dietetics based on epigenomics (epigenome dietetics)

• Project/Area Number: 16H03046
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Eating habits
• Research Institution: The University of Tokushima
• Principal Investigator: TAKETANI Yutaka 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (30263825)
• Co-Investigator(Kenkyū-buntansha): 増田 真志 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (50754488) ; 山本 浩範 仁愛大学, 人間生活学部, 教授 (60314861)
• Research Collaborator: NARASAKI Yoko ; FUKUDA Shiori ; HAYASHI Mayu ; KISHIMOTO Maki ; NII Sachi ; IMI Yukiko ; NIIDA Yuki ; ODA Naoko
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000); Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
• Keywords: リン / 慢性腎臓病 / エピゲノム / ライフステージ / 高リン食 / 食事調査 / 遺伝子 / ゲノム / トランスレーショナルリサーチ / klotho / 骨

Outline of Final Research Achievements

Overintake of phosphate, which is an essential nutrient, has been concerned about the risk factor associated with cariovascular disease and all-cause mortality. In this study, we have explored a novel biomarker reflecting continuous overintake of phosphate in mice and validated the marker in human. We demonstrated that fibroblast growth factor 23 (FGF23), which is a phosphaturic hormone, can be a good biomarker reflecting continuous overintake of phosphate. In addition, we developed a convenient evaluation tool to assess the daily intake of phosphate in human. This tool and the marker, FGF23, are useful tool to determine adequate recommended dietary allowance of phosphate and for nutritional education in chronic kidney disease patients who are required dietary phosphate restriction.

Academic Significance and Societal Importance of the Research Achievements

リン過剰摂取は、慢性腎臓病患者で問題になるだけでなく、健常者においても心血管疾患の発症リスクや総死亡リスクと関連することが指摘されている。リン過剰摂取とこれらの疾患の発症リスクや総死亡リスクとの間をつなぐメカニズムにエピゲノム修飾の存在が推定される。本研究で見出された指標を用い研究を進めることで、健康増進を進めるための適切なリン摂取量の設定あるいは慢性腎臓病患者の適切な食事指導に活用されることが期待される。

Research Products

• [Journal Article] Regulation of α-Klotho Expression by Dietary Phosphate During Growth Periods (2019)
  • Author(s): Fukuda-Tatano Shiori、Yamamoto Hironori、Nakahashi Otoki、Yoshikawa Ryouhei、Hayashi Mayu、Kishimoto Maki、Imi Yukiko、Yamanaka-Okumura Hisami、Ohnishi Kohta、Masuda Masashi、Taketani Yutaka
  • Journal Title: Calcified Tissue International Volume: 印刷中 Issue: 6 Pages: 667-678
  • DOI: 10.1007/s00223-019-00525-0
  • NAID: 130008058761
  • Peer Reviewed / Open Access
• [Journal Article] High phosphate diet suppresses lipogenesis in white adipose tissue (2018)
  • Author(s): Imi Yukiko、Yabiki Norie、Abuduli Maerjianghan、Masuda Masashi、Yamanaka-Okumura Hisami、Taketani Yutaka
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 63 Issue: 3 Pages: 181-191
  • DOI: 10.3164/jcbn.17-141
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Sterol regulatory element binding protein 1 trans-activates 25-hydroxy vitamin D3 24-hydroxylase gene expression in renal proximal tubular cells (2018)
  • Author(s): Kagawa Tomohiro、Kozai Mina、Masuda Masashi、Harada Nagakatsu、Nakahashi Otoki、Tajiri Mari、Yoshikawa Ryouhei、Nakao Mari、Takei Yuichiro、Iwano Masayuki、Takeda Eiji、Taketani Yutaka、Yamamoto Hironori
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 500 Issue: 2 Pages: 275-282
  • DOI: 10.1016/j.bbrc.2018.04.058
  • Peer Reviewed / Open Access
• [Journal Article] Investigation of dose‐dependent effects of fat on blood glucose, serum insulin, and appetite sensation (2018)
  • Author(s): Yamaguchi Chise、Yamanaka‐Okumura Hisami、Esumi Haruka、Masuda Masashi、Katayama Takafumi、Taketani Yutaka
  • Journal Title: The Journal of Medical Investigation Volume: 65 Issue: 3.4 Pages: 203-207
  • DOI: 10.2152/jmi.65.203
  • NAID: 130007495849
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access
• [Journal Article] The age-related changes of dietary phosphate responsiveness in plasma 1,25-dihydroxyvitamin D levels and renal Cyp27b1 and Cyp24a1 gene expression is associated with renal α-Klotho gene expression in mice (2018)
  • Author(s): Yoshikawa R, Yamamoto H, Nakahashi O, Kagawa T, Tajiri M, Nakao M, Fukuda S, Arai H, Masuda M, Iwano M, Takeda E, Taketani Y.
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 62 Issue: 1 Pages: 68-74
  • DOI: 10.3164/jcbn.17-20
  • NAID: 130006301221
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Dietary phosphate exacerbates intestinal inflammation in experimental colitis (2017)
  • Author(s): Kohei Sugihara, Masashi Masuda, Mari Nakao, Maerjianghan Abuduli, Yukiko Imi, Naoko Oda, Toshiya Okahisa, Hironori Yamamoto, Eiji Takeda, Yutaka Taketani
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 61 Issue: 2 Pages: 91-99
  • DOI: 10.3164/jcbn.16-117
  • NAID: 130006038748
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Presentation] 妊娠後期の食餌性リン負荷が仔の将来におけるリン代謝調節系に及ぼす影響 (2018)
  • Author(s): 岸本麻希、福田詩織、林眞由、増田真志、竹谷豊
  • Organizer: 第5回日本栄養改善学会四国支部学術集会
• [Presentation] 妊娠前における食餌性リン負荷が新生仔マウスのリン代謝調節系に及ぼす影響 (2018)
  • Author(s): 林眞由、福田詩織、増田真志、竹谷豊、山本浩範
  • Organizer: 第36回日本骨代謝学会学術集会
• [Presentation] ライフステージにおけるリン摂取量がリン・ビタミンD代謝調節系に及ぼす影響 (2018)
  • Author(s): 福田 詩織, 林 眞由, 岸本 麻希, 増田 真志, 山本 浩範, 竹谷 豊
  • Organizer: 第91回日本生化学会大会
• [Presentation] High phosphate diet before pregnancy dysregulates phosphate metabolism in neonatal offspring mice. (2018)
  • Author(s): Mayu Hayashi, Shiori Fukuda, Maki Kishimoto, Hironori Yamamoto, Masashi Masuda, Yutaka Taketani
  • Organizer: American Society of Nephrology, Kidney week 2018
  • Int'l Joint Research
• [Presentation] Continuous ingestion of the different phosphorus bioavailability meal in healthy Japanese. (2018)
  • Author(s): Yoko Narasaki, Michiyo Yamasaki, Misaki Katsumoto, Sayaka Matsuura, Mayumi Morinishi, Tomomi Nakagawa, Mami Matsuno, Tsuneyuki Noda, Yutaka Taketani
  • Organizer: XIX International Congress on Nutrition and Metabolism in Renal Disease
  • Int'l Joint Research
• [Presentation] リンと心血管疾患：細胞からヒトでの研究まで (2018)
  • Author(s): 竹谷豊
  • Organizer: 第6回日本腎栄養代謝研究会学術集会・エデュケーショナルセミナー
  • Invited
• [Presentation] 高リン食摂取は腸内環境を変化させる (2017)
  • Author(s): 織田奈央子、杉原恒平、吉本亜由美、上番増喬、増田真志、奥村仙示、竹谷豊
  • Organizer: 第71回日本栄養・食糧学会大会
• [Presentation] 骨格筋脂質代謝異常が慢性腎臓病に伴うProtein-Wasting(CKD-PEW)を誘発する (2017)
  • Author(s): 新井田裕樹、増田真志、吉澤和香、Ilimulati Yimamu、吉田里沙、甲谷芹奈、奥村仙示、河合慶親、竹谷豊、山本浩範
  • Organizer: 第71回日本栄養・食糧学会大会
• [Presentation] リン生体利用率の異なる食品が活性型ビタミンD値に及ぼす影響 (2017)
  • Author(s): 楢崎瑶子、山崎通世、勝本美咲、松浦明香、森西真由美、中川倫未、松野真美、野田恒行、奥村仙示、竹谷豊
  • Organizer: 日本ビタミン学会第69回大会
• [Presentation] 高リン食による白色脂肪組織の減少 (2017)
  • Author(s): 伊美友紀子、矢引紀江、Maerjianghan Abuduli、増田真志、奥村仙示、竹谷豊
  • Organizer: 日本ビタミン学会第69回大会
• [Presentation] リンと心血管疾患：リン制限は寿命を延伸する？ (2017)
  • Author(s): 竹谷豊、福田詩織、増田真志、奥村仙示
  • Organizer: 第17回日本抗加齢医学会総会
  • Invited
• [Presentation] 食事性リンとリン負荷指数 (2017)
  • Author(s): 竹谷豊、楢崎瑶子、奥村仙示、増田真志
  • Organizer: 第62回日本透析医学会学術集会・総会
  • Invited
• [Presentation] 一塩基多型rs1697421は尿中リン排泄以外の経路を介して 食後血清リン濃度上昇に影響する (2017)
  • Author(s): 新居沙知、楢崎瑶子、奥村仙示、竹谷豊
  • Organizer: 第5回日本腎栄養代謝研究会
• [Presentation] 食事性リンとリン負荷指数 (2016)
  • Author(s): 竹谷豊、楢崎遥子、山本浩範
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2016-07-23
  • Invited
• [Book] リンの事典 (2017)
  • Author(s): 大竹久夫、竹谷豊、山本浩範、他155名
  • Total Pages: 360
  • Publisher: 朝倉書店