Yamaguchi, Shintaro

写真a

Affiliation

School of Medicine, Medical Education Center ( Shinanomachi )

Position

Associate Professor (Non-tenured)
Scopus Paper Info  
Paper Count: 57 Citation Count: 1149 h-index: 16

Click to view the Scopus page. The data was downloaded from Scopus API in March 29, 2026, via http://api.elsevier.com and http://www.scopus.com .

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Career 【 Display / hide 】

  • 1999.04
    -
    2005.03

    Keio university school of medicine

  • 2009.04
    -
    2013.03

    Keio university school of medicine

  • 2014.10
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    2017.03

    Washington university school of medicine

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Academic Background 【 Display / hide 】

  • 2005.03

    慶應義塾大学, 医学部

    Graduated

  • 2013.03

    慶應義塾大学, 医学研究科大学院博士課程

    Graduated

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Academic Degrees 【 Display / hide 】

  • 医学博士, 慶應義塾大学, 2013.03

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Licenses and Qualifications 【 Display / hide 】

  • 日本内科学会総合内科専門医・指導医, 2008

  • 日本腎臓学会専門医・指導医, 2013

  • 日本内分泌学会専門医, 2017

  • 日本透析医学会専門医

  • 日本糖尿病学会専門医, 2023.12

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Research Areas 【 Display / hide 】

  • Life Science / Metabolism and endocrinology (予防医学、老年医学、インスリン抵抗性、NAD合成系)

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Papers 【 Display / hide 】

  • Vascular Endothelial NAMPT-Mediated NAD+ Biosynthesis Regulates Angiogenesis and Cardiometabolic Functions in Male Mice

    Shotaro Kosugi, Shintaro Yamaguchi, Ken Nishioka, Taichi Nagahisa, Yasuhiro Watanabe, Daiki Kojima, Kenji Kaneko, Ryunosuke Mitsuno, Ran Nakamichi, Yoshinaga Kawano, Kenichiro Kinouchi, Koichiro Homma, Takeshi Kanda, Junichiro Irie, Kazutoshi Miyashita, Toshiaki Monkawa, Jun Yoshino, Hiroshi Itoh, Kaori Hayashi

    Aging Cell .  2025.11

    Joint Work, Corresponding author, Accepted

  • Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men

    Yamaguchi, S., Irie, J., Mitsuishi, M., Uchino, Y., Nakaya, H., Takemura, R., Inagaki, E., Kosugi, S., Okano, H., Yasui, M., Tsubota, K., Hayashi, K., Yoshino, J. and Itoh, H.

    Endocr J 71 ( 2 ) 153 - 169 2024

    Lead author, Corresponding author,  ISSN  09188959

    　View Summary

    Obesity and aging are major risk factors for several life-threatening diseases. Accumulating evidence from both rodents and humans suggests that the levels of nicotinamide adenine dinucleotide (NAD(+)), a regulator of many biological processes, declines in multiple organs and tissues with aging and obesity. Administration of an NAD(+) intermediate, nicotinamide mononucleotide (NMN), replenishes intracellular NAD(+) levels and mitigates aging- and obesity-associated derangements in animal models. In this human clinical study, we aimed to investigate the safety and effects of 8-week oral administration of NMN on biochemical, metabolic, ophthalmologic, and sleep quality parameters as well as on chronological alterations in NAD(+) content in peripheral tissues. An 8-week, single-center, single-arm, open-label clinical trial was conducted. Eleven healthy, middle-aged Japanese men received two 125-mg NMN capsules once daily before breakfast. The 8-week NMN supplementation regimen was well-tolerated; NAD(+) levels in peripheral blood mononuclear cells increased over the course of NMN administration. In participants with insulin oversecretion after oral glucose loading, NMN modestly attenuated postprandial hyperinsulinemia, a risk factor for coronary artery disease (n = 3). In conclusion, NMN overall safely and effectively boosted NAD(+) biosynthesis in healthy, middle-aged Japanese men, showing its potential for alleviating postprandial hyperinsulinemia.

  • Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice.

    Yamaguchi S, Franczyk MP, Chondronikola M, Qi N, Gunawardana SC, Stromsdorfer KL, Porter LC, Wozniak DF, Sasaki Y, Rensing N, Wong M, Piston DW, Klein S, Yoshino J.

    Proc Natl Acad Sci U S A. (Proceedings of the National Academy of Sciences of the United States of America)  116 ( 47 ) 23822 - 23828 2019.11

    Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  00278424

    　View Summary

    Nicotinamide adenine dinucleotide (NAD(+)) is a critical coenzyme for cellular energy metabolism. The aim of the present study was to determine the importance of brown and white adipose tissue (BAT and WAT) NAD(+) metabolism in regulating whole-body thermogenesis and energy metabolism. Accordingly, we generated and analyzed adipocyte-specific nicotinamide phosphoribosyltransferase (Nampt) knockout (ANKO) and brown adipocyte-specific Nampt knockout (BANKO) mice because NAMPT is the rate-limiting NAD(+) biosynthetic enzyme. We found ANKO mice, which lack NAMPT in both BAT and WAT, had impaired gene programs involved in thermogenesis and mitochondrial function in BAT and a blunted thermogenic (rectal temperature, BAT temperature, and whole-body oxygen consumption) response to acute cold exposure, prolonged fasting, and administration of β-adrenergic agonists (norepinephrine and CL-316243). In addition, the absence of NAMPT in WAT markedly reduced adrenergic-mediated lipolytic activity, likely through inactivation of the NAD(+)-SIRT1-caveolin-1 axis, which limits an important fuel source fatty acid for BAT thermogenesis. These metabolic abnormalities were rescued by treatment with nicotinamide mononucleotide (NMN), which bypasses the block in NAD(+) synthesis induced by NAMPT deficiency. Although BANKO mice, which lack NAMPT in BAT only, had BAT cellular alterations similar to the ANKO mice, BANKO mice had normal thermogenic and lipolytic responses. We also found NAMPT expression in supraclavicular adipose tissue (where human BAT is localized) obtained from human subjects increased during cold exposure, suggesting our finding in rodents could apply to people. These results demonstrate that adipose NAMPT-mediated NAD(+) biosynthesis is essential for regulating adaptive thermogenesis, lipolysis, and whole-body energy metabolism.

  • Intestinal Epithelial NAD+ Biosynthesis Regulates GLP-1 Production and Postprandial Glucose Metabolism in Mice

    Nagahisa, T., Yamaguchi, S., Kosugi, S., Homma, K., Miyashita, K., Irie, J., Yoshino, J. and Itoh, H.

    Endocrinology 163 ( 4 )  2022.02

    Corresponding author, Accepted,  ISSN  0013-7227

    　View Summary

    Obesity is associated with perturbations in incretin production and whole-body glucose metabolism, but the precise underlying mechanism remains unclear. Here, we tested the hypothesis that nicotinamide phosphoribosyltransferase (NAMPT), which mediates the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a key regulator of cellular energy metabolism, plays a critical role in obesity-associated intestinal pathophysiology and systemic metabolic complications. To this end, we generated a novel mouse model, namely intestinal epithelial cell-specific Nampt knockout (INKO) mice. INKO mice displayed diminished glucagon-like peptide-1 (GLP-1) production, at least partly contributing to reduced early-phase insulin secretion and postprandial hyperglycemia. Mechanistically, loss of NAMPT attenuated the Wnt signaling pathway, resulting in insufficient GLP-1 production. We also found that diet-induced obese mice had compromised intestinal NAMPT-mediated NAD+ biosynthesis and Wnt signaling pathway, associated with impaired GLP-1 production and whole-body glucose metabolism, resembling the INKO mice. Finally, administration of a key NAD+ intermediate, nicotinamide mononucleotide (NMN), restored intestinal NAD+ levels and obesity-associated metabolic derangements, manifested by a decrease in ileal Proglucagon expression and GLP-1 production as well as postprandial hyperglycemia in INKO and diet-induced obese mice. Collectively, our study provides mechanistic and therapeutic insights into intestinal NAD+ biology related to obesity-associated dysregulation of GLP-1 production and postprandial hyperglycemia.

  • Diurnal variation in PDK4 expression is associated with plasma free fatty acid availability in people.

    Shintaro Yamaguchi, Anna C Moseley, Paloma Almeda-Valdes Kelly L Stromsdorfer, Michael P Franczyk, Adewole L Okunade,Bruce W Patterson, Samuel Klein, Jun Yoshino

    J Clin Endocrinol Metab. (Journal of Clinical Endocrinology and Metabolism)  103 ( 3 ) 1068 - 1076 2018.03

    Research paper (scientific journal), Joint Work, Lead author, Accepted,  ISSN  0021972X

    　View Summary

    CONTEXT: Many biological pathways involved in regulating substrate metabolism display rhythmic oscillation patterns. In rodents, clock genes regulate circadian rhythms of metabolic genes and substrate metabolism. However, the interrelationships among substrate metabolism, metabolic genes, and clock genes have not been fully explored in people. OBJECTIVE: We tested the hypothesis that the diurnal expression pattern of pyruvate dehydrogenase kinase 4 (PDK4), a key metabolic enzyme involved in fuel switching between glucose and free fatty acids (FFAs), is associated with plasma FFA concentration and clock genes. DESIGN AND METHODS: We analyzed peripheral blood mononuclear cells (PBMCs), subcutaneous adipose tissue, and plasma samples obtained serially during 24 hours from metabolically healthy women (n = 10) and evaluated the interrelationships among PDK4, plasma FFA, and clock genes. We also determined the potential mechanisms responsible for PDK4 transcriptional regulation by using primary human PBMCs and adipocytes. RESULTS: We found that PDK4 diurnal expression patterns were similar in PBMCs and adipose tissue (ρ = 0.84, P < 0.001). The diurnal variation in PBMC PDK4 expression correlated more strongly with plasma FFA and insulin (ρ = 0.86 and 0.63, respectively, both P < 0.001) concentrations than clock genes. Data obtained from primary culture experiments demonstrated that FFAs directly induced PDK4 gene expression, at least in part through activation of peroxisome proliferator-activated receptor α. CONCLUSIONS: Our results suggest that plasma FFA availability is an important regulator of diurnal expression patterns of PDK4, and we identify a novel interaction between plasma FFA and cellular diurnal rhythms in regulating substrate metabolism.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • 老化関連疾患における NAD⁺合成系・ミトコン ドリアサーチュン SIRT3 の生理学的重要性と治療標的としての可能性.

    山口慎太郎、吉野純

    日本臨床  2016

    Article, review, commentary, editorial, etc. (scientific journal), Joint Work

  • ヒトにおける概日リズムとインスリン感受性制 御機構のクロストーク.

    山口慎太郎、吉野純

     2016

    Article, review, commentary, editorial, etc. (scientific journal), Joint Work

  • 老化関連疾患におけるNAD+合成系の役割と創薬標的としての可能性

    山口 慎太郎，吉野 純

    生化学  2015

    Article, review, commentary, editorial, etc. (scientific journal), Joint Work

  • 6年次臨床実習終了後に行ったプロフェッショナリズムの自己評価と同僚評価の現状とその乖離の検討

    山口 慎太郎, 春田 淳志, 門川 俊明

    医学教育 ((一社)日本医学教育学会)  55 ( Suppl. ) 245 - 245 2024.07

    ISSN  0386-9644

  • 原発性アルドステロン症における腎洞脂肪蓄積の臨床的意義の検証

    満野 竜ノ介, 金子 賢司, 中村 俊文, 児島 大輝, 水谷 洋佑, 畔上 達彦, 山口 慎太郎, 山田 祥岳, 陣崎 雅弘, 木内 謙一郎, 吉野 純, 林 香

    日本腎臓学会誌 ((一社)日本腎臓学会)  66 ( 4 ) 629 - 629 2024.06

    ISSN  0385-2385

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 腎血管内皮および足細胞NAD合成系を標的とした老化に伴う腎硬化症発症予防法の開発

    2025.04
    -
    2030.03

    基盤研究(C), Principal investigator

  • 脂肪組織血管新生能を標的とした血管内皮NAD賦活化による肥満2型糖尿病発症予防

    2021.04
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    2025.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (C), Principal investigator

  • 腸管NAMPT-NAD合成系を標的としたNMNによるインスリン抵抗性予防法の開発

    2018.04
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    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

  • ヒトES・iPS細胞由来腎臓・血管前駆細胞と脱細胞化技術の融合による新規腎臓再生

    2014.04
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    2016.03

    文部科学省・日本学術振興会, 科学研究費助成事業, 山口 慎太郎, 若手研究(B), 補助金, 研究代表者, No Setting

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