Integrated understanding of phosphate-sensing mechanism and its application for lifestyle disease prevention

• Project/Area Number: 25282022
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Eating habits
• Research Institution: Jin-ai University
• Principal Investigator: Yamamoto Hironori 仁愛大学, 人間生活学部, 教授 (60314861)
• Co-Investigator(Kenkyū-buntansha): 岩野 正之 福井大学, 医学部, 教授 (20275324) ; 竹谷 豊 徳島大学, 大学院医歯薬学研究部, 教授 (30263825)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000); Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000); Fiscal Year 2013: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
• Keywords: リン / 感受性遺伝子 / 生活習慣病 / 日内リズム / 発達段階 / 遺伝子発現

Outline of Final Research Achievements

In this study, we identified a novel phosphorus susceptibility gene by omics analysis and elucidated the molecular basis of the mechanism, and constructed a database of developmental stage / diurnal rhythm specific phosphorus sensing. As a result, as a phosphorus-sensitive gene, AMPK and Keap 1 which is regulator of intracellular signal molecules of Nrf 2 protein, clock protein, and these circadian related genes and detoxification related genes, and the regulation of expression mechanism of FGF23 and alpha-klotho essential for phosphorus; vitamin D metabolism and vitamin D metabolism-related enzymes. In addition, we developed and established a treatment method based on the phosphorus content in the meal to prevent the onset / development of lifestyle diseases targeting developmental stage and diurnal rhythm.

Research Products

• [Journal Article] Effects of dietary phosphate on glucose and lipid metabolism. (2016)
  • Author(s): Abuduli M, Ohminami H, Otani T, Kubo H, Ueda H, Kawai Y, Masuda M, Yamanaka-Okumura H, Sakaue H, Yamamoto H, Takeda E, Taketani Y.
  • Journal Title: Am J Physiol Endocrinol Metab. Volume: 310 Issue: 7 Pages: 526-538
  • DOI: 10.1152/ajpendo.00234.2015
  • Peer Reviewed / Open Access
• [Journal Article] Transcriptional activation of the wild-type and mutant vitamin D receptors by vitamin D3 analogs. (2016)
  • Author(s): Futawaka K, Tagami T, Fukuda Y, Koyama R, Nushida A, Nezu S, Yamamoto H, Imamoto M, Kasahara M, Moriyama K.
  • Journal Title: J Mol Endocrinol. Volume: 57 Issue: 1 Pages: 23-32
  • DOI: 10.1530/jme-16-0048
  • Peer Reviewed / Open Access
• [Journal Article] Dietary phosphate supplementation delays the onset of iron deficiency anemia and affects iron status in rats. (2015)
  • Author(s): Nakao M, Yamamoto H, Nakahashi O, Ikeda S, Abe K, Masuda M, Ishiguro M, Iwano M, Takeda E, Taketani Y.
  • Journal Title: Nutrition research Volume: 35(11) Issue: 11 Pages: 1016-1024
  • DOI: 10.1016/j.nutres.2015.09.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Down-regulation of renal type IIa sodium-dependent phosphate co-transporter during lipopolysaccharide-induced acute inflammation (2014)
  • Author(s): Ikeda S, Yamamoto H, Masuda M, Miyamoto K(他9名)
  • Journal Title: Am J Physiol Renal Physiol Volume: 306(7) Issue: 7 Pages: 744-750
  • DOI: 10.1152/ajprenal.00474.2013
  • Peer Reviewed / Open Access
• [Journal Article] Dietary combination of sucrose and linoleic acid causes skeletal muscle metabolic abnormalities in Zucker fatty rats through specific modification of fatty acid composition (2014)
  • Author(s): Hirokazu Ohminami, Kikuko Amo, Yutaka Taketani, Kazusa Sato, Makiko Fukaya, Takashi Uebanso, Hidekazu Arai, Megumi Koganei, Hajime Sasaki, Hisami Yamanaka-Okumura, Hironori Yamamoto, Eiji Takeda
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 55 Issue: 1 Pages: 15-25
  • DOI: 10.3164/jcbn.14-11
  • NAID: 130004466759
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed / Open Access
• [Journal Article] Elevated fibroblast growth factor 23 exerts its effects on placenta and regulates vitamin D metabolism in pregnancy of hyp mice (2014)
  • Author(s): Okano T(12), 他13人
  • Journal Title: J Bone Miner Res Volume: 印刷中 Issue: 7 Pages: 0-0
  • DOI: 10.1002/jbmr.2186
  • Peer Reviewed / Open Access
• [Journal Article] 小児疾患および成人疾患からみたビタミンD栄養学 (2014)
  • Author(s): 武田英二、奥村仙示、竹谷豊、山本浩範
  • Journal Title: ビタミン Volume: 88(10) Pages: 499-506
  • NAID: 110009891160
  • Peer Reviewed
• [Journal Article] Short-term dietary phosphate restriction up-regulates ileal fibroblast growth factor 15 gene expression in mice (2014)
  • Author(s): Nakahashi O, Yamamoto H, Miyamoto K(他8名)
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 54 Issue: 2 Pages: 102-108
  • DOI: 10.3164/jcbn.13-109
  • NAID: 130004879348
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Increasing dietary phosphorus intake from food additives: potential for negative impact on bone health. (2014)
  • Author(s): Takeda Y, Yamamoto H, Yamanaka-Okumura H, Taketani Y
  • Journal Title: Adv Nutr Volume: 5 Issue: 1 Pages: 92-97
  • DOI: 10.3945/an.113.004002
  • Peer Reviewed
• [Journal Article] Induction of the hepatic stearoyl-CoA desaturase 1 gene in offspring after isocaloric administration of high fat sucrose diet during gestation (2013)
  • Author(s): Wanjihia VW, Ohminami H, Taketani Y, Amo K, Yamanaka-Okumura H, Yamamoto H, Takeda E
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 53 Issue: 3 Pages: 150-157
  • DOI: 10.3164/jcbn.13-48
  • NAID: 130004466725
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Journal Article] Hypercholesterolemia and effects of high cholesterol diet in type IIa sodium-dependent phosphate co-transporter (Npt2a) deficient mice (2013)
  • Author(s): Tanaka S, Yamamoto H, Nakahashi O, Ishiguro M, Takei Y, Masuda M, Kozai M, Ikeda S, Taketani Y, Miyamoto K, Takeda E.
  • Journal Title: The Journal of Medical Investigation Volume: 60 Issue: 3.4 Pages: 191-196
  • DOI: 10.2152/jmi.60.191
  • NAID: 130004822682
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed
• [Journal Article] Gene expression profiling in peripheral white blood cells in response to the intake of food with different glycemic index using a DNA microarray. (2013)
  • Author(s): Kawakami Y, Yamanaka-Okumura H, Sakuma M, Mori Y, Adachi C, Matsumoto Y, Sato T, Yamamoto H, Taketani Y, Katayama T, Takeda E.
  • Journal Title: J Nutrigenet Nutrigenomics. Volume: 6(3) Issue: 3 Pages: 154-168
  • DOI: 10.1159/000354247
  • Peer Reviewed
• [Journal Article] Dietary phosphate restriction induces hepatic lipid accumulation through dysregulation of cholesterol metabolism in mice. (2013)
  • Author(s): Tanaka S, Yamamoto H, Nakahashi O, Kagawa T, Ishiguro M, Masuda M, Kozai M, Ikeda S, Taketani Y, Takeda E.
  • Journal Title: Nutr Res. Volume: 33(7) Issue: 7 Pages: 586-593
  • DOI: 10.1016/j.nutres.2013.05.004
  • Peer Reviewed
• [Presentation] 食餌性リン負荷が鉄欠乏性貧血（IDA）の発症・進展に及ぼす影響 (2016)
  • Author(s): 山本浩範、中橋乙起、石黒真理子、竹谷豊
  • Organizer: 第63回日本栄養改善学会学術総会
  • Place of Presentation: 青森県青森市 リンクステーション青森
  • Year and Date: 2016-09-07
• [Presentation] α-klotho発現およびビタミンD代謝に及ぼす加齢と食餌性リンの影響 (2016)
  • Author(s): 山本浩範、吉川亮平、福田詩織、中橋乙起、石黒真理子、増田真志、武田英二、竹谷豊
  • Organizer: 日本ビタミン学会第68回大会
  • Place of Presentation: 富山県富山市 富山国際会議場
  • Year and Date: 2016-06-17
• [Presentation] ビタミンD代謝の概日リズムの分子機構の解明と時間治療への応用 (2016)
  • Author(s): 山本浩範、岡村友理香、石黒真理子、中橋乙起、青木菜摘、柴田重信、岩野正之、竹谷豊
  • Organizer: 日本栄養食糧学会 第70回大会
  • Place of Presentation: 兵庫県西宮市 武庫川女子大学
  • Year and Date: 2016-05-13
• [Presentation] 食事性リンが炎症性腸疾患の病態および腸管バリア機能に及ぼす影響 (2016)
  • Author(s): 杉原康平、増田真志、中尾真理、Maerjianghan Abuduli、石田陽子、山本浩範、武田英二、竹谷豊
  • Organizer: 日本栄養食糧学会 第70回大会
  • Place of Presentation: 兵庫県西宮市 武庫川女子大学
  • Year and Date: 2016-05-13
• [Presentation] Regulation of α-Klotho Expression by Dietary Phosphate during Growth Periods (2015)
  • Author(s): Shiori Fukuda, Hironori Yamamoto, Masashi Masuda, Mari Nakao, Yutaka Taketani
  • Organizer: 米国腎臓学会議 (American Society of Nephrology (ASN) Kidney Week 2015 Annual Meeting
  • Place of Presentation: サンディエゴコンベンションセンター（アメリカ合衆国)
  • Year and Date: 2015-11-03
  • Int'l Joint Research
• [Presentation] マウスにおいて短期間の食餌性リン制限は回腸Fibroblast growth factor 15遺伝子発現量を増加させる (2015)
  • Author(s): 中橋乙起、山本浩範、田中更沙、竹谷豊 栄養学雑誌
  • Organizer: 第62回日本栄養改善学会
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 2015-09-24
• [Presentation] 食餌性リンによる腎α-klotho発現制御と異所性石灰化の発症 (2015)
  • Author(s): 福田詩織、山本浩範、中尾真理、武田英二、竹谷豊
  • Organizer: 第33回日本骨代謝学会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2015-07-23
• [Presentation] 食餌性リンによる鉄欠乏性貧血の進展および鉄代謝に及ぼす影響 (2015)
  • Author(s): 中尾真理、山本浩範、福田詩織、竹谷豊、武田英二
  • Organizer: 第33回日本骨代謝学会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2015-07-23
• [Presentation] 急性炎症時における生体ビタミンD代謝変動の解析 (2015)
  • Author(s): 山本浩範、池田翔子、糸魚川玲子、加藤愛理、小寺里奈、源甲斐優美、石黒真理子、竹谷豊、武田英二
  • Organizer: 日本ビタミン学会第67回大会
  • Place of Presentation: 奈良県新公会堂（奈良）
  • Year and Date: 2015-06-05
• [Presentation] Induction of intact and C-terminal FGF23 levels and its gene expression in lipopolysaccharide-induced acute inflammation (2015)
  • Author(s): Hironori Yamamoto, Soko Ikeda, Mari Nakao, Yutaka Taketani, Eiji Takeda
  • Organizer: 12th Asian Congress of Nutrition (ACN2015)
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] Effects of dietary phosphate on the progression of anemia in iron deficient rats (2015)
  • Author(s): Mari Nakao, Hironori Yamamoto, Otoki Nakahashi, Soko Ikeda, Kotaro Abe, Shiori Fukuda, Yutaka Taketani, Eiji Takeda
  • Organizer: 12th Asian Congress of Nutrition (ACN2015)
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] Down-regulation of renal type IIa sodium-dependent phosphate co-transporter during lipopolysaccharide-induced acute inflammation (2014)
  • Author(s): Hironori Yamamoto, Shoko Ikeda, Otoki Nakahashi, Yutaka Taketani, Masayuki Iwano, Ken-ichi Miyamoto, Eiji Takeda
  • Organizer: American Society of Nephrology (ASN) Kidney Week 2014 Annual Meeting
  • Place of Presentation: フィラデルフィア、ペンシルベニア州、アメリカ合衆国
  • Year and Date: 2014-11-12 – 2014-11-17
• [Presentation] Association with Fetuin-A and Ectopic Calcification in α-klotho Mutant Mice (2014)
  • Author(s): Hironori Yamamoto, Nozomi Yokoyama, Rina Onishi, Shiori Fukuda, Otoki Nakahashi, Yuichiro Takei, Yutaka Taketani, Eiji Takeda
  • Organizer: 第36回米国骨代謝学会議 (ASBMR 2014)
  • Place of Presentation: ヒューストン、テキサス州、アメリカ合衆国
  • Year and Date: 2014-09-12 – 2014-09-17
• [Presentation] 肝臓脂質蓄積とコレステロール代謝に及ぼす リンの影響 (2014)
  • Author(s): 田中更沙、山本浩範、伊藤美紀子、竹谷豊
  • Organizer: 第61回日本栄養改善学会
  • Place of Presentation: 横浜市、神奈川県
  • Year and Date: 2014-08-20 – 2014-08-22
• [Presentation] FGF23/α-klothoシグナル異常による異所性石灰化発症とFetuin-Aの発現変動 (2014)
  • Author(s): 山本浩範、大西里奈、福田詩織、竹井悠一郎、竹谷豊、武田英二
  • Organizer: 第32回日本骨代謝学会
  • Place of Presentation: 大阪市、大阪府
  • Year and Date: 2014-07-24 – 2014-07-26
• [Presentation] ビタミンD代謝の日内リズムの分子機構の解明及び時間治療への応用 (2014)
  • Author(s): 山本浩範、田尻真梨、中橋乙起、香西美奈、香川智博、竹谷豊、武田英二
  • Organizer: 日本ビタミン学会第66回大会
  • Place of Presentation: 姫路市、兵庫県
  • Year and Date: 2014-06-13 – 2014-06-14
• [Presentation] 食餌性リンによる腎α-Klotho発現制御と異所性石灰化の発症 (2014)
  • Author(s): 福田詩織、山本浩範、中橋乙起、池田翔子、横山望、吉川亮平、大西里奈、竹谷豊、武田英二
  • Organizer: 第68回日本栄養・食糧学会大会
  • Place of Presentation: 札幌市、北海道
  • Year and Date: 2014-05-30 – 2014-05-31
• [Presentation] 甲状腺ホルモンは腎臓25水酸化ビタミンD3-1α水酸化酵素遺伝子(CYP27B1)の転写抑制により血中活性型ビタミンD濃度を低下させる (2013)
  • Author(s): 山本浩範、香西美奈、香川知博、原田永勝、中橋乙起、池田翔子、竹谷豊、武田英二
  • Organizer: 第67回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋大学、愛知県
• [Presentation] リン補給は鉄欠乏性貧血の進展を予防する (2013)
  • Author(s): 中尾真理、山本浩範、阿部航太郎、中橋乙起、池田翔子、竹谷豊、武田英二
  • Organizer: 第67回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋大学、愛知県
• [Presentation] マウス腎αKlotho発現に与える加齢および食餌性リンの影響 (2013)
  • Author(s): 吉川亮平、山本浩範、香川智博、中橋乙起、横山望、大西里奈、池田翔子、竹谷豊、武田英二
  • Organizer: 第67回日本栄養・食糧学会大会
  • Place of Presentation: 名古屋大学、愛知県
• [Presentation] 「ミネラル摂取と老化制御：Klotho研究から見えるミネラル管理の重要性」 (2013)
  • Author(s): 山本浩範
  • Organizer: 第67回日本栄養・食糧学会大会 シンポジウム
  • Place of Presentation: 名古屋大学、愛知県
  • Invited
• [Presentation] 糖尿病時におけるビタミンD・カルシウム代謝異常の分子機構の解明 (2013)
  • Author(s): 山本浩範、田尻真梨、中橋乙起、香西美奈、香川智博、竹谷豊、武田英二
  • Organizer: 日本ビタミン学会第65回大会
  • Place of Presentation: 一橋大学・一橋講堂（旧学術総合センター）、東京都
• [Presentation] 25－ヒドロキシビタミンD3-24－水酸化酵素CYP24A1の新たな発現調節因子の同定 (2013)
  • Author(s): 香川智博、山本浩範、香西美奈、原田永勝、向原理恵、竹谷豊、武田英二
  • Organizer: 日本ビタミン学会第65回大会
  • Place of Presentation: 一橋大学・一橋講堂（旧学術総合センター）、東京都
• [Presentation] 小腸および腎臓におけるカルシウム輸送機構とCKD (2013)
  • Author(s): 山本浩範
  • Organizer: 第56回日本腎臓病学会学術総会 ワークショップ
  • Place of Presentation: 東京国際フォーラム、東京都
  • Invited
• [Presentation] Thyroid hormones decrease plasma 1α,25­dihydroxyvitamin D levels through transcriptional repression of the renal 25-hydroxyvitamin D3 1α-hydroxylase gene (CYP27B1) (2013)
  • Author(s): Hironori Yamamoto, Mina Kozai, Tomohiro Kagawa, Shoko Ikeda, Nagakatsu Harada, Otoki Nakahashi, Yutaka Taketani, Eiji Takeda
  • Organizer: 2nd Joint Meeting of the International Bone and Mineral Society and the Japanese Society for Bone and Mineral Research IBMS
  • Place of Presentation: 神戸コンベンションセンター、兵庫県
• [Presentation] Thyroid Hormones decrease plasma 1α, 25-dihydroxyvitamin D levels through directly and indirectly transrepression of the renal 25-hydroxyvitamin D3 1α-hydroxylase gene (CYP27B1) (2013)
  • Author(s): Hironori Yamamoto, Mina Kozai, Tomohiro Kagawa, Nagakatsu Harada, Shoko Ikeda, Otoki Nakahashi, Yutaka Taketani, Ken-ichi Takeyama, Shigeaki Kato, Eiji Takeda
  • Organizer: 第35回米国骨代謝学会議 (ASBMR 2013)
  • Place of Presentation: ボルチモアコンベンションセンター、メリーランド、米国
• [Presentation] Fetal Stage-Specific Mineral Metabolism in Hyp Mice Is Associated with Effects of FGF23 on Placenta (2013)
  • Author(s): Yasuhisa Ohhata, Miwa Yamazaki, Masanobu Kawai, Kanako Tachikawa, Tomoko Koinuma, Kazuaki Miyagawa, Akihito Kimoto, Masahiro Nakayama, Noriyuki Namba, Hironori Yamamoto, Keiichi Ozono, Toshimi Michigami
  • Organizer: 第35回米国骨代謝学会議 (ASBMR 2013)
  • Place of Presentation: ボルチモアコンベンションセンター、メリーランド、米国
• [Presentation] Thyroid Hormones Decrease Plasma 1α,25-Dihydroxyvitamin D Levels through Transcriptional Repression of the Renal 25-Hydroxyvitamin D3 1α-Hydroxylase Gene (CYP27B1) (2013)
  • Author(s): Hironori Yamamoto, Mina Kozai, Tomohiro Kagawa, Otoki Nakahashi, Shoko Ikeda, Rina Onishi, Yutaka Taketani, Eiji Takeda
  • Organizer: 米国腎臓学会議 (American Society of Nephrology (ASN) Kidney Week 2013 Annual Meeting)
  • Place of Presentation: Georgia World Congress Center、アトランタ、米国)