Exploration of genomic signals controlling energy metabolism and its application to lifestyle-related diseases

• Project/Area Number: 15H03092
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied health science
• Research Institution: University of Tsukuba
• Principal Investigator: Yahagi Naoya 筑波大学, 医学医療系, 准教授 (60420246)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2016: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
• Keywords: エネルギー代謝 / 栄養 / ゲノム / 転写 / 転写複合体 / 核内情報 / 生活習慣病

Outline of Final Research Achievements

Energy metabolic control of an individual is performed with high accuracy referring to the nucleotide sequence of the genome. How do we respond to fasting and feeding? From this point of view, we have tried to comprehensively understand glucose and lipid metabolism. In this study, the in vivo Ad-luc analytical method and the TFEL scan method, which we have independently developed over the past few years, temporally and spatially resolve various signals controlling energy metabolism. As a result of searching for an unknown nuclear information processing mechanism responsible for energy metabolism, a part of the processing mechanism became clear, which can lead to the development of therapeutic strategies for lifestyle / obesity-related diseases in the future.

Research Products

• [Int'l Joint Research] Case Cardiovascular Research Institute(米国)
• [Int'l Joint Research] Case Cardiovascular Research Institute(米国)
• [Journal Article] A candidate functional SNP rs7074440 in TCF7L2 alters gene expression through C-FOS in hepatocytes. (2018)
  • Author(s): Piao X, Yahagi N, Takeuchi Y, Aita Y, Murayama Y, Sawada Y, Shikama A, Masuda Y, Nishi-Tatsumi M, Kubota M, Izumida Y, Sekiya M, Matsuzaka T, Nakagawa Y, Sugano Y, Iwasaki H, Kobayashi K, Yatoh S, Suzuki H, Yagyu H, Kawakami Y, Shimano H.
  • Journal Title: FEBS Letters Volume: 592(3) Pages: 422-433
  • DOI: 10.1002/1873-3468.12975
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry (2017)
  • Author(s): Sawada Yoshikazu、Izumida Yoshihiko、Takeuchi Yoshinori、Aita Yuichi、Wada Nobuhiro、Li EnXu、Murayama Yuki、Piao Xianying、Shikama Akito、Masuda Yukari、Nishi-Tatsumi Makiko、Kubota Midori、Sekiya Motohiro、Matsuzaka Takashi、Nakagawa Yoshimi、Shimano Hitoshi、Yahagi Naoya
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 493 Pages: 40-45
  • DOI: 10.1016/j.bbrc.2017.09.081
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Hormone-sensitive Lipase in Leptin-Promoted Fat Loss and Glucose Lowering (2017)
  • Author(s): Takanashi M, Taira Y, Okazaki S, Takase S, Kimura T, Li CC, Xu PF, Noda A, Sakata I, Kumagai H, Ikeda Y, Iizuka Y, Yahagi N, Shimano H, Osuga JI, Ishibashi S, Kadowaki T, Okazaki H
  • Journal Title: J Atheroscler Thromb Volume: 24 Issue: 11 Pages: 1105-1116
  • DOI: 10.5551/jat.39552
  • NAID: 130006191603
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed
• [Journal Article] Elovl6 Deficiency Improves Glycemic Control in Diabetic db / db Mice by Expanding β-Cell Mass and Increasing Insulin Secretory Capacity (2017)
  • Author(s): Zhao Hui、Matsuzaka Takashi、Nakano Yuta、Motomura Kaori、Tang Nie、Yokoo Tomotaka、Okajima Yuka、Han Song-iee、Takeuchi Yoshinori、Aita Yuichi、Iwasaki Hitoshi、Yatoh Shigeru、Suzuki Hiroaki、Sekiya Motohiro、Yahagi Naoya、Nakagawa Yoshimi、Sone Hirohito、Yamada Nobuhiro、Shimano Hitoshi
  • Journal Title: Diabetes. Volume: 66 Pages: 1833-1846
  • DOI: 10.2337/db16-1277
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The selective PPARα modulator K-877 efficiently activates the PPARα pathway and improves lipid metabolism in mice (2017)
  • Author(s): Takei K, Han SI, Murayama Y, Satoh A, Oikawa F, Ohno H, Osaki Y, Matsuzaka T, Sekiya M, Iwasaki H, Yatoh S, Yahagi N, Suzuki H, Yamada N, Nakagawa Y, Shimano H.
  • Journal Title: J Diabetes Investig Volume: in press Pages: 446-452
  • DOI: 10.1111/jdi.12621
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A key role of nuclear factor Y in the refeeding response of fatty acid synthase in adipocytes. (2017)
  • Author(s): Nishi-Tatsumi M, Yahagi N, Takeuchi Y, Toya N, Takarada A, Murayama Y, Aita Y, Sawada Y, Piao X, Oya Y, Shikama A, Masuda Y, Kubota M, Izumida Y, Matsuzaka T, Nakagawa Y, Sekiya M, Iizuka Y, Kawakami Y, Kadowaki T, Yamada N, Shimano H.
  • Journal Title: FEBS Letters Volume: 591 Pages: 40-45
  • DOI: 10.1002/1873-3468.12620
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] KLF15 Enables Rapid Switching between Lipogenesis and Gluconeogenesis during Fasting. (2016)
  • Author(s): Takeuchi Y, Yahagi N, Aita Y, Murayama Y, Sawada Y, Piao X, Toya N, Oya Y, Shikama A, Takarada A, Masuda Y, Nishi M, Kubota M, Izumida Y, Yamamoto T, Sekiya M, Matsuzaka T, Nakagawa Y, Urayama O, Kawakami Y, Iizuka Y, Gotoda T, Itaka K, Kataoka K, Nagai R, Kadowaki T, Yamada N, Lu Y, Jain MK, and Shimano H
  • Journal Title: Cell Reports Volume: 16 Pages: 2373-2386
  • DOI: 10.1016/j.celrep.2016.07.069
  • NAID: 120007129426
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα. (2016)
  • Author(s): Nakagawa Y, Satoh A, Tezuka H, Han SI, Takei K, Iwasaki H, Yatoh S, Yahagi N, Suzuki H, Iwasaki Y, Sone H, Matsuzaka T, Yamada N, Shimano H.
  • Journal Title: Scientific Reports Volume: 6 Pages: 39182-39182
  • DOI: 10.1038/srep39182
  • NAID: 120007135285
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducing Npc1l1 expression. (2016)
  • Author(s): Kikuchi T, Orihara K, Oikawa F, Han SI, Kuba M, Okuda K, Satoh A, Osaki Y, Takeuchi Y, Aita Y, Matsuzaka T, Iwasaki H, Yatoh S, Sekiya M, Yahagi N, Suzuki H, Sone H, Nakagawa Y, Yamada N, Shimano H.
  • Journal Title: Mol Metab Volume: 5 Pages: 1092-1102
  • DOI: 10.1016/j.molmet.2016.09.004
  • NAID: 120007129266
  • Peer Reviewed / Open Access
• [Journal Article] Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice. (2016)
  • Author(s): Suzuki-Kemuriyama N, Matsuzaka T, Kuba M, Ohno H, Han SI, Takeuchi Y, Isaka M, Kobayashi K, Iwasaki H, Yatoh S, Suzuki H, Miyajima K, Nakae D, Yahagi N, Nakagawa Y, Sone H, Yamada N, Shimano H.
  • Journal Title: PLoS One Volume: 11(6)
  • DOI: 10.1371/journal.pone.0157580
  • NAID: 120007135350
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Hyperlipidemia and hepatitis in liver-specific CREB3L3 knockout micegenerated using a one-step CRISPR/Cas9 system. (2016)
  • Author(s): Nakagawa Y, Oikawa F, Ohno H, Yagishita Y, Satoh A, Osaki Y, Takei K, Kikuchi T, Song-iee H, Mizuno S, Matsuzaka T, Iwasaki H, Kobayashi K, Yatoh S, Yahagi N, Suzuki H, Sone H, Takahashi S, Yamada N, Shimano H.
  • Journal Title: Scientific Report Volume: 6 Pages: 27857-27857
  • DOI: 10.1038/srep27857
  • NAID: 120007135376
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Identification of human ELOVL5 enhancer regions controlled by SREBP. (2015)
  • Author(s): Shikama A, Shinozaki H, Takeuchi Y, Matsuzaka T, Aita Y, Murayama T, Sawada Y, Piao X, Toya N, Oya Y, Takarada A, Masuda Y, Nishi M, Kubota M, Izumida Y, Nakagawa Y, Iwasaki H, Kobayashi K, Yatoh S, Suzuki H, Yagyu H, Kawakami Y, Yamada N, Shimano H, Yahagi N.
  • Journal Title: Biochem Biophys Res Commun. Volume: 465(4) Pages: 857-63
  • DOI: 10.1016/j.bbrc.2015.08.101
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a (2015)
  • Author(s): Kuba M, Matsuzaka T, Matsumori R, Saito R, Kaga N, Taka H, Ikehata K, Okada N,
  • Journal Title: Scientific Reports Volume: 5 Pages: 1-14
  • DOI: 10.1038/srep17604
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Skeletal muscle-specific HMG-CoA reductase knockout mice exhibit rhabdomyolysis: A model for statin-induced myopathy. (2015)
  • Author(s): Osaki Y, Nakagawa Y, Miyahara S, Iwasaki H, Ishii A, Matsuzaka T, Kobayashi K, Yatoh S, Takahashi A, Yahagi N, Suzuki H, Sone H, Ohashi K, Ishibashi S, Yamada N, Shimano H
  • Journal Title: Biochemical and Biophysical Research Communications. Volume: 466(3) Pages: 536-40
  • DOI: 10.1016/j.bbrc.2015.09.065
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Circulating Malondialdehyde-Modified LDL-Related Variables and Coronary Artery Stenosis in Asymptomatic Patients with Type 2 Diabetes (2015)
  • Author(s): Fujihara K, Suzuki H, Sato A, Kodama S, Heianza Y, Saito K, Iwasaki H, Kobayashi K, Yatoh S, Takahashi A, Yahagi N, Yagyu H, Sone H, Shimano H.
  • Journal Title: J Diabetes Res. Volume: 印刷中 Pages: 507245-507245
  • DOI: 10.1155/2015/507245
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 「食の代謝・進化から迫る生命の戦略」：エネルギー欠乏への対応戦略 (2018)
  • Author(s): 矢作直也
  • Organizer: 日本農芸化学会2018年度大会
  • Invited
• [Presentation] 「栄養シグナルと生体応答」：「栄養シグナル」による遺伝子発現調節 (2017)
  • Author(s): 矢作直也
  • Organizer: 第39回日本臨床栄養学会総会・第38回日本臨床栄養協会総会
  • Invited
• [Presentation] KLF15は絶食時に中性脂肪合成から糖新生への速やかな切り替えを可能にする (2017)
  • Author(s): 武内謙憲, 矢作直也, 會田雄一, 村山友樹, 朴賢英, 沢田義一, 志鎌明人, 升田紫,泉田欣彦, 関谷元博, 松坂賢, 中川嘉, 川上康, 島野仁
  • Organizer: 第39回日本臨床栄養学会総会・第38回日本臨床栄養協会総会
• [Presentation] 中性脂肪合成を制御する転写複合体の解明 (2017)
  • Author(s): 矢作直也
  • Organizer: 第49回日本動脈硬化学会総会・学術集会
  • Invited
• [Presentation] 脂肪酸分画を診療に生かす (2017)
  • Author(s): 矢作直也
  • Organizer: 第49回日本動脈硬化学会総会・学術集会
  • Invited
• [Presentation] KLF15は絶食時において脂質代謝と糖代謝を抑制する重要な因子である (2017)
  • Author(s): 武内謙憲, 矢作直也, 會田雄一, 村山友樹, 沢田義一, 朴賢英, 志鎌明人, 升田紫, 泉田欣彦, 関谷元博, 松坂賢, 中川嘉, 川上康, 山田信博, 島野仁
  • Organizer: 第49回日本動脈硬化学会総会・学術集会
• [Presentation] 糖質・脂質酸エネルギー基質動員に関する協調制御機構の解明 (2017)
  • Author(s): 和田亘弘, 泉田欣彦, 矢作直也, 升田紫, 李恩旭, 沢田義一, 武内謙憲, 島野仁, 門脇孝
  • Organizer: 第71回日本栄養・食糧学会大会
• [Presentation] 多価不飽和脂肪酸（PUFA）によるSREBP-1特異的な抑制機序の解明 (2017)
  • Author(s): 升田紫, 矢作直也, 武内謙憲, 沢田義一, 朴賢英, 會田雄一, 戸谷直樹, 大屋友華里, 志鎌明人, 西真貴子, 泉田欣彦, 飯塚陽子, 位高啓史, 片岡一則, 島野仁, 門脇孝
  • Organizer: 第60回日本糖尿病学会年次学術集会
• [Presentation] 2型糖尿病に関連したTCF7L2遺伝子の一塩基多型の機能分析 (2017)
  • Author(s): 朴賢英, 矢作直也, 武内謙憲, 會田雄一, 村山友樹, 沢田義一, 志鎌明人, 升田紫,泉田欣彦, 関谷元博, 松坂賢, 中川嘉, 川上康, 島野仁
  • Organizer: 第60回日本糖尿病学会年次学術集会
• [Presentation] 脂肪酸エネルギー基質動員の優先性を制御する分子基盤の探求 新規エネルギーセンサーの探索 (2017)
  • Author(s): 泉田欣彦, 和田亘弘, 矢作直也, 武内謙憲, 李恩旭, 升田紫, 沢田義一, 戸谷直樹, 朴賢英, 會田雄一, 志鎌明人, 飯塚陽子, 島野仁, 門脇孝
  • Organizer: 第60回日本糖尿病学会年次学術集会
• [Presentation] KLF15は絶食時において脂質代謝と糖代謝を制御する重要な因子である (2017)
  • Author(s): 武内謙憲, 矢作直也, 會田雄一, 村山友樹, 沢田義一, 朴賢英, 志鎌明人, 升田紫,泉田欣彦, 関谷元博, 松坂賢, 中川嘉, 川上康, 山田信博, 島野仁
  • Organizer: 第60回日本糖尿病学会年次学術集会
• [Presentation] 選択的動脈内カルシウム注入試験にてインスリノーマが明らかとなった高度肥満合併多発性内分泌腫瘍症1型の1例 (2017)
  • Author(s): 志鎌明人, 松村えりか, 久芳素子, 菅野洋子, 岩崎仁, 関谷元博, 矢藤繁, 矢作直也, 鈴木浩明, 島野仁
  • Organizer: 第90回日本内分泌学会学術総会
• [Presentation] Effect of sodium-glucose cotransporter 2 (SGLT2) inhibition on weight loss is partly mediated by liver-brain-adipose neurocircuitry. (2017)
  • Author(s): 沢田義一, 泉田欣彦, 武内謙憲, 會田雄一, 和田亘弘, 李恩旭, 村山友樹, 朴賢英, 志鎌明人, 升田紫, 西真貴子, 久保田みどり, 関谷元博, 松坂賢, 中川嘉, 島野仁, 矢作直也
  • Organizer: 第40回日本分子生物学会年会・第90回日本生化学会大会(ConBio2017)
• [Presentation] KLF15は絶食時において脂質代謝と糖代謝を制御する重要な因子である (2016)
  • Author(s): 武内謙憲, 矢作直也, 會田雄一, 村山友樹, 沢田義一, 朴賢英, 戸谷直樹, 大屋友華里, 志鎌明人, 西真貴子, 升田紫, 久保田みどり, 泉田欣彦, 関谷元博, 松坂賢, 中川嘉, 川上康, 山田信博, 島野仁
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2016-11-30
• [Presentation] 大血管障害予防に向けたLDL-C管理目標値 (2016)
  • Author(s): 矢作直也
  • Organizer: 第31回日本糖尿病合併症学会
  • Place of Presentation: 仙台
  • Year and Date: 2016-10-07
  • Invited
• [Presentation] Fumctional analysis of TCF7L2 SNPs associated with type 2 diabetes. (2016)
  • Author(s): Piao X, Yahagi N, Takeuchi Y, Aita Y, Murayama Y, Sawada Y, Toya N, Oya Y, Shikama A, Takarada A, Masuda Y, Nishi M, Kubota M, Izumida Y, Sekiya M, Matsuzaka T, Nakagawa Y, Kawakami Y, Yamada N, Shimano H.
  • Organizer: Tsukuba Global Science Week 2016
  • Place of Presentation: つくば
  • Year and Date: 2016-09-17
  • Int'l Joint Research
• [Presentation] n-3系多価不飽和脂肪酸と脂質異常症・動脈硬化 (2016)
  • Author(s): 矢作直也
  • Organizer: 第48回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 東京
  • Year and Date: 2016-07-14
  • Invited
• [Presentation] apoE遺伝子プロモーターのTFEL scan解析 (2016)
  • Author(s): 志鎌明人，武内謙憲，村山友樹，和田亘弘，李恩旭，朴賢英，沢田義一，會田雄一，戸谷直樹，升田紫，西真貴子，久保田みどり，泉田欣彦，松坂賢，中川嘉，岩崎仁，小林和人，矢藤繁，鈴木浩明，野牛宏晃，川上康，山田信博，門脇孝，島野仁，矢作直也
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都
  • Year and Date: 2016-05-19
• [Presentation] ゲノム多型解析に基づく2型糖尿病リスク分析・予防サービスによる健康指導効果の検証 (2016)
  • Author(s): 升田紫，矢作直也，武内謙憲，會田雄一，朴賢英，村山友樹，和田亘弘，李恩旭，沢田義一，戸谷直樹，志鎌明人，西真貴子，久保田みどり，泉田欣彦，中村健一郎，田村祐子，岸暁子，上村夕香理，益子友恵，水野由子，前田士郎，新井洋由，門脇孝，山崎力，徳渕慎一郎
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都
  • Year and Date: 2016-05-19
• [Presentation] 新規エネルギー・センサーによる脂肪酸系エネルギー動員機序の探求 (2016)
  • Author(s): 泉田欣彦，和田亘弘，矢作直也，武内謙憲，李恩旭，升田紫，沢田義一，戸谷直樹，朴賢英，會田雄一，志鎌明人，飯塚陽子，島野仁，門脇孝
  • Organizer: 第59回日本糖尿病学会年次学術集会
  • Place of Presentation: 京都
  • Year and Date: 2016-05-19
• [Presentation] 摂食・絶食サイクルの転写調節機構 (2015)
  • Author(s): 矢作直也, 武内謙憲, 西真貴子, 志鎌明人, 戸谷直樹, 沢田義一, 村山友樹, 和田亘弘, 李恩旭, 朴賢英, 會田雄一, 大屋友華里, 古賀俊介, 宝田亜矢子, 升田紫, 久保田みどり, 泉田欣彦
  • Organizer: BMB2015(第38回日本分子生物学会年会・第88回日本生化学会大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] 多価不飽和脂肪酸（PUFA）によるSREBP-1特異的な抑制機序の解明 (2015)
  • Author(s): 升田紫, 矢作直也, 武内謙憲, 和田亘弘, 李恩旭, 沢田義一, 朴賢英, 會田雄一, 戸谷直樹, 志鎌明人, 西真貴子, 久保田みどり, 泉田欣彦, 飯塚陽子, 位高啓史, 片岡一則, 山田信博, 島野仁, 門脇孝
  • Organizer: 第36回日本肥満学会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-02
• [Presentation] In vivo Ad-luc analyses of Leptin gene expression. (2015)
  • Author(s): Toya N, Yahagi N, Takeuchi Y, Nishi M, Sawada Y, Piao XY, Aita Y, Oya Y, Shikama A, Masuda Y, Kubota M, Izumida Y, Matsuzaka T, Nakagawa Y, Yamada N, Kadowaki T, Shimano H
  • Organizer: Tsukuba Global Science Week 2015
  • Place of Presentation: つくば
  • Year and Date: 2015-09-28
  • Int'l Joint Research
• [Presentation] 脂肪組織におけるin vivo Ad-luc法によるfatty acid synthaseのプロモーター解析 (2015)
  • Author(s): 西真貴子, 矢作直也, 武内謙憲, 志鎌明人, 戸谷直樹, 大屋友華里, 朴賢英, 會田雄一, 沢田義一, 松坂賢, 中川嘉, 升田紫, 泉田欣彦, 飯塚陽子, 山田信博, 門脇孝, 島野仁
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 下関
  • Year and Date: 2015-05-21
• [Book] 実験医学増刊「遺伝子制御の新たな主役 栄養シグナル」 (2016)
  • Author(s): 矢作直也
  • Total Pages: 231
  • Publisher: 羊土社
• [Book] 疾患モデルの作製と利用―脂質代謝異常と関連疾患 上巻 (2015)
  • Author(s): 尾池雄一, 佐々木雄彦, 村上誠, 矢作直也 編
  • Total Pages: 477
  • Publisher: エル・アイ・シー
• [Book] 疾患モデルの作製と利用―脂質代謝異常と関連疾患 下巻 (2015)
  • Author(s): 尾池雄一, 佐々木雄彦, 村上誠, 矢作直也 編
  • Total Pages: 413
  • Publisher: エル・アイ・シー
• [Remarks] 筑波大学医学医療系 ニュートリゲノミクスリサーチグループ
  • URL: http://nyahagi.wixsite.com/ngrg