WAKI Hironori

写真a

Affiliation

Graduate School of Medicine  Doctorial Course in Medicine  Bioregulatory Medicine  Department of Metabolism and Endocrinology

Mail Address

E-mail address

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Research Interests 【 display / non-display 】

  • 代謝

  • 糖尿病

  • 遺伝子

  • 脂肪細胞

  • 肥満

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Graduating School 【 display / non-display 】

  • 　
    -
    1997.03

    The University of Tokyo   Faculty of Medicine   Graduated

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Graduate School 【 display / non-display 】

  • 　
    -
    2003.03

    The University of Tokyo  Graduate School, Division of Medicine  Doctor's Course  Completed

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Campus Career 【 display / non-display 】

  • 2021.06
    -
    Now

    Akita University   Graduate School of Medicine   Doctorial Course in Medicine   Bioregulatory Medicine   Department of Metabolism and Endocrinology   Professor  

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External Career 【 display / non-display 】

  • 2019.09
    -
    2021.05

    Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo   Associate Professor  

  • 2018.11
    -
    2019.08

    Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo   Lecturer  

  • 2016.09
    -
    2018.10

    Department of Molecular Sciences on Diabetes, Graduate School of Medicine, the University of Tokyo   Project Associate Professor  

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Research Areas 【 display / non-display 】

  • Life Science / Molecular biology  / Molecular biology

  • Life Science / Nutrition science and health science

  • Life Science / Cell biology  / Cellular biology

  • Life Science / Genetics  / Genomics

  • Life Science / Metabolism and endocrinology  / Diabetes and Metabolic Diseases

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Research Achievements 【 display / non-display 】

    ◆Original paper【 display / non-display 】

  • GLP-1 receptor signaling restores aquaporin 4 subcellular polarization in reactive astrocytes and promotes amyloid β clearance in a mouse model of Alzheimer's disease.

    Kana Sasaki, Hiroki Fujita, Takehiro Sato, Shunske Kato, Yuya Takahashi, Yukio Takeshita, Takashi Kanda, Takashi Saito, Takamori C Saido, Satoko Hattori, Yasukazu Hozumi, Yuichiro Yamada, Hironori Waki

    Biochemical and biophysical research communications   741   151016 - 151016   2024.11

    Research paper (journal)  

    The physiological actions of a gut hormone, glucagon-like peptide-1 (GLP-1), in Alzheimer's disease (AD) brain remain poorly understood, although GLP-1 receptor (GLP-1R) expression in this organ has been shown in several experimental studies. Therefore, we explored whether the GLP-1R signaling promotes the clearance of amyloid β (Aβ) (1-42) which is a core pathological hallmark of AD, focusing on the water channel protein aquaporin 4 (AQP4) localized to astrocyte endfeet perivascular membranes in intact brain. First, we confirmed that Glp1r mRNA is predominantly expressed at perivascular site of astrocytes in normal mouse cerebral cortex through in situ hybridization analysis. Next, we observed that 20-week subcutaneous administration of a GLP-1R agonist (GLP-1RA) liraglutide significantly reduced Aβ (1-42) accumulation in the cerebral cortex and improved spatial working memory in an AD mouse model, AppNL-G-F/NL-G-F mice. Furthermore, our current data revealed that the 4-week liraglutide treatment relocalized subcellular AQP4 in morphologically injured reactive astrocytes of AppNL-G-F/NL-G-F mice to the cell surface perivascular site through PKA-mediated AQP4 phosphorylation. Such translocation of phosphorylated AQP4 to astrocyte cell surface following incubation with liraglutide was observed also in the present in vitro study using the cell line in which AQP4 cDNA was introduced into immortalized human astrocyte. These results suggest that enhanced intracerebral GLP-1R signaling following peripheral administration of GLP-1RA restores AQP4 subcellular polarization in reactive astrocytes and would promote Aβ excretion possibly through increasing AQP4-mediated intracerebral water flux in the brain in AD.

    DOI PubMed

  • Transcription factor PATZ1 promotes adipogenesis by controlling promoter regulatory loci of adipogenic factors.

    Sanil Patel, Khatanzul Ganbold, Chung Hwan Cho, Juwairriyyah Siddiqui, Ramazan Yildiz, Njeri Sparman, Shani Sadeh, Christy M Nguyen, Jiexin Wang, Julian P Whitelegge, Susan K Fried, Hironori Waki, Claudio J Villanueva, Marcus M Seldin, Shinya Sakaguchi, Wilfried Ellmeier, Peter Tontonoz, Prashant Rajbhandari

    Nature communications   15 ( 1 ) 8533 - 8533   2024.10  [Refereed]

    Research paper (journal)  

    White adipose tissue (WAT) is essential for lipid storage and systemic energy homeostasis. Understanding adipocyte formation and stability is key to developing therapies for obesity and metabolic disorders. Through a high-throughput cDNA screen, we identified PATZ1, a POZ/BTB and AT-Hook Containing Zinc Finger 1 protein, as an important adipogenic transcription factor. PATZ1 is expressed in human and mouse adipocyte precursor cells (APCs) and adipocytes. In cellular models, PATZ1 promotes adipogenesis via protein-protein interactions and DNA binding. PATZ1 ablation in mouse adipocytes and APCs leads to a reduced APC pool, decreased fat mass, and hypertrophied adipocytes. ChIP-Seq and RNA-seq analyses show that PATZ1 supports adipogenesis by interacting with transcriptional machinery at the promoter regions of key early adipogenic factors. Mass-spec results show that PATZ1 associates with GTF2I, with GTF2I modulating PATZ1's function during differentiation. These findings underscore PATZ1's regulatory role in adipocyte differentiation and adiposity, offering insights into adipose tissue development.

    DOI PubMed

  • Recurrent nocturnal hypoglycemic hemiplegia: a case report and review of the literature.

    Hanako Toyama, Kazuyuki Takahashi, Tatsunori Shimizu, Izumi Otaka, Sakiko Abe, Shunsuke Kato, Sayaka Ando, Takehiro Sato, Tsukasa Morii, Hiroki Fujita, Hironori Waki

    Endocrine journal     2024.02  [Refereed]

    Research paper (journal)  

    A 67-year-old man with type 1 diabetes, Cronkhite-Canada syndrome, and membranous nephropathy who received insulin therapy was admitted to our hospital with right hemiplegia and dysarthria. Brain magnetic resonance imaging revealed a lesion with a high diffusion-weighted imaging signal and low apparent diffusion coefficient signal in the posterior limb of the left internal capsule. He was hypoglycemic with a blood glucose level of 56 mg/dL (3.1 mmol/L). Following glucose administration, the patient's symptoms resolved within several hours. The patient experienced similar transient hypoglycemic hemiplegia at midnight, three times within 10 days. In a literature review of 170 cases of hypoglycemic hemiplegia, 26 cases of recurrent hemiplegia were investigated. Recurrent hypoglycemic hemiplegia occurs more frequently on the right side than on the left side, and most recurrences occur within approximately a week, almost exclusively at midnight and in the early morning. We speculate that hypoglycemia-associated autonomic failure may be involved in the nocturnal recurrence of episodes. In our patient, depleted endogenous insulin secretion and lipodystrophy at the injection site, may have acted as additional factors, leading to severe hypoglycemia despite the absence of apparent autonomic neuropathy. Clinically, it is important to recognize hypoglycemia as a cause of hemiplegia to avoid unnecessary intervention and to maintain an appropriate blood glucose level at midnight and early in the morning to prevent recurrent hypoglycemic hemiplegia.

    DOI PubMed

  • Efficacy of StepAdd, a Personalized mHealth Intervention Based on Social Cognitive Theory to Increase Physical Activity Among Patients With Type 2 Diabetes Mellitus: Protocol for a Randomized Controlled Trial.

    Kayo Waki, Yuya Tsurutani, Hironori Waki, Syunpei Enomoto, Kosuke Kashiwabara, Akira Fujiwara, Kazuki Orime, Sho Kinguchi, Toshimasa Yamauchi, Nobuhito Hirawa, Kouichi Tamura, Yasuo Terauchi, Masaomi Nangaku, Kazuhiko Ohe

    JMIR research protocols   13   e53514   2024.02

    Research paper (journal)  

    BACKGROUND: Increasing physical activity improves glycemic control in patients with type 2 diabetes (T2D). Mobile health (mHealth) interventions have been proven to increase exercise, but engagement often fades with time. As the use of health behavior theory in mHealth design can increase effectiveness, we developed StepAdd, an mHealth intervention based on the constructs of social cognitive theory (SCT). StepAdd improves exercise behavior self-efficacy and self-regulation through the use of goal-setting, barrier-identifying, and barrier-coping strategies, as well as automatic feedback functions. A single-arm pilot study of StepAdd among 33 patients with T2D showed a large increase in step count (mean change of 4714, SD 3638 daily steps or +86.7%), along with strong improvements in BMI (mean change of -0.3 kg/m2) and hemoglobin A1c level (mean change of -0.79 percentage points). OBJECTIVE: In this study, we aim to investigate the efficacy and safety of StepAdd, an mHealth exercise support system for patients with T2D, via a large, long, and controlled follow-up to the pilot study. METHODS: This is a randomized, open-label, multicenter study targeting 160 patients with T2D from 5 institutions in Japan with a 24-week intervention. The intervention group will record daily step counts, body weight, and blood pressure using the SCT-based mobile app, StepAdd, and receive feedback about these measurements. In addition, they will set weekly step count goals, identify personal barriers to walking, and define strategies to overcome these barriers. The control group will record daily step counts, body weight, and blood pressure using a non-SCT-based placebo app. Both groups will receive monthly consultations with a physician who will advise patients regarding lifestyle modifications and use of the app. The 24-week intervention period will be followed by a 12-week observational period to investigate the sustainability of the intervention's effects. The primary outcome is between-group difference in the change in hemoglobin A1c values at 24 weeks. The secondary outcomes include other health measures, measurements of steps, measurements of other behavior changes, and assessments of app use. The trial began in January 2023 and is intended to be completed in December 2025. RESULTS: As of September 5, 2023, we had recruited 44 patients. We expect the trial to be completed by October 8, 2025, with the follow-up observation period being completed by December 31, 2025. CONCLUSIONS: This trial will provide important evidence about the efficacy of an SCT-based mHealth intervention in improving physical activities and glycemic control in patients with T2D. If this study proves the intervention to be effective and safe, it could be a key step toward the integration of mHealth as part of the standard treatment received by patients with T2D in Japan. TRIAL REGISTRATION: Japan Registry of Clinical Trials (JRCT) jRCT2032220603; https://rctportal.niph.go.jp/en/detail?trial_id=jRCT2032220603. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53514.

    DOI PubMed

  • Gastric inhibitory polypeptide receptor antagonism suppresses intramuscular adipose tissue accumulation and ameliorates sarcopenia.

    Yuya Takahashi, Hiroki Fujita, Yusuke Seino, Satoko Hattori, Shihomi Hidaka, Tsuyoshi Miyakawa, Atsushi Suzuki, Hironori Waki, Daisuke Yabe, Yutaka Seino, Yuichiro Yamada

    Journal of cachexia, sarcopenia and muscle     2023.10

    Research paper (journal)  

    BACKGROUND: Intramuscular adipose tissue (IMAT) formation derived from muscle fibro-adipogenic progenitors (FAPs) has been recognized as a pathological feature of sarcopenia. This study aimed to explore whether genetic and pharmacological gastric inhibitory polypeptide (GIP) receptor antagonism suppresses IMAT accumulation and ameliorates sarcopenia in mice. METHODS: Whole body composition, grip strength, skeletal muscle weight, tibialis anterior (TA) muscle fibre cross-sectional area (CSA) and TA muscle IMAT area were measured in young and aged male C57BL/6 strain GIP receptor (Gipr)-knockout (Gipr-/- ) and wild-type (Gipr+/+ ) mice. FAPs isolated from lower limb muscles of 12-week-old Gipr+/+ mice were cultured with GIP, and their differentiation into mature adipocytes was examined. Furthermore, TA muscle IMAT area and fibre CSA were measured in untreated Gipr-/- mice and GIP receptor antagonist-treated Gipr+/+ mice after glycerol injection into the TA muscles. RESULTS: Body composition analysis revealed that 104-week-old Gipr-/- mice had a greater proportion of lean tissue mass (73.7 ± 1.2% vs. 66.5 ± 2.7%, P < 0.05 vs. 104-week-old Gipr+/+ mice) and less adipose tissue mass (13.1 ± 1.3% vs. 19.4 ± 2.6%, P < 0.05 vs. 104-week-old Gipr+/+ mice). Eighty-four-week-old Gipr-/- mice exhibited increases in grip strength (P < 0.05), weights of TA (P < 0.05), soleus (P < 0.01), gastrocnemius (P < 0.05) and quadriceps femoris (P < 0.01) muscles, and average TA muscle fibre CSA (P < 0.05) along with a reduction in TA muscle IMAT area assessed by the number of perilipin-positive cells (P < 0.0001) compared with 84-week-old Gipr+/+ mice. Oil Red O staining analysis revealed 1.6- and 1.7-fold increased adipogenesis in muscle FAPs cultured with 10 and 100 nM of GIP (P < 0.01 and P < 0.001 vs. 0 nM of GIP, respectively). Furthermore, both untreated Gipr-/- mice and GIP receptor antagonist-treated Gipr+/+ mice for 14 days after glycerol injection into the TA muscles at 12 weeks of age showed reduced TA muscle IMAT area (1.39 ± 0.38% and 2.65 ± 0.36% vs. 6.54 ± 1.30%, P < 0.001 and P < 0.01 vs. untreated Gipr+/+ mice, respectively) and increased average TA muscle fibre CSA (P < 0.01 and P < 0.05 vs. untreated Gipr+/+ mice, respectively). CONCLUSIONS: GIP promotes the differentiation of muscle FAPs into adipocytes and its receptor antagonism suppresses IMAT accumulation and promotes muscle regeneration. Pharmacological GIP receptor antagonism may serve as a novel therapeutic approach for sarcopenia.

    DOI PubMed

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    ◆Introduction and explanation【 display / non-display 】

  • The Latest Science of Fat Cells

    Hironori Waki

    Medical View Point ( Iji Publishing Co., Ltd. )  44 ( 9 ) 6 - 6   2023.09

    Introduction and explanation (commerce magazine)  

  • One point advice---How much is your best weight?

    Hironori Waki

    Medical Practice   40 ( 5 ) 800 - 800   2023.05

    Introduction and explanation (scientific journal)  

  • Team approach of bariatric and metabolic surgeries (topics editor)

    Hironori Waki, Kunihisa Kobayashi

    DM Ensemble ( Nikkei Medical )  11 ( 2 ) 6 - 6   2022.08

    Introduction and explanation (scientific journal)  

  • Genetics in obesity and obeesity stigma

    Hironori Waki

    DM Ensemble ( Nikkei Medical )  11 ( 2 ) 36 - 37   2022.08

    Introduction and explanation (scientific journal)  

  • Brown and beige aipocytes

    Hironori Waki

    Japanese Journal of Clinical Medicine   80 ( 4 ) 607 - 701   2022.04

    Introduction and explanation (scientific journal)  

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    ◆Other【 display / non-display 】

  • Vision Transformer–based Tinea Unguium Classification Approach Using Foot Images

    Miura Kakeru, Zou Min, Sato Takehiro, Waki Hironori, Kageyama Yoichi

    Proceedings of IIAE Annual Conference ( The Institute of Industrial Applications Engineers )  2024 ( 0 ) 67 - 68   2024

    DOI CiNii Research

  • CNN-SVM-Based Tinea Unguium Classification Approach to Telemedicine System

    Miura Kakeru, Zou Min, Sato Takehiro, Waki Hironori, Kageyama Yoichi

    Proceedings of IIAE Annual Conference ( The Institute of Industrial Applications Engineers )  2023 ( 0 ) 23 - 24   2023

    In recent years, the number of patients with diabetes mellitus has increased. Moreover, the prevalence of diabetes among older age groups in Japan is notably higher, indicating a growing proportion of patients with diabetes. Diabetic foot complications manifests in some patients with diabetes mellitus; hence, timely identification of the symptoms associated with diabetic feet is crucial for preventing severe complications. It is imperative for patients to observe their feet regularly; however, recognizing diabetic foot symptoms can be challenging for individuals without medical expertise owing to the variability of such symptoms. In this study, we focused on tinea unguium as a case type and utilized machine learning to classify images of tinea unguium and normal feet. The evaluation results showed that the combination of ResNet-50 and a support vector machine yielded the best performance when applied to a dataset of the acquired images of the nail regions the feet.

    DOI CiNii Research

  • CNN-SVM-Based Tinea Unguium Classification Approach to Telemedicine System

    三浦翔流, ZOU Min, 佐藤雄大, 脇裕典, 景山陽一

    産業応用工学会全国大会講演論文集(Web)   2023   2023

    J-GLOBAL

  • Effects of GLP-1 Receptor Agonist on Changes in the Gut Bacterium and the Underlying Mechanisms

      49 ( 1 ) 37 - 44   2022.06

    DOI CiNii Research

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Books 【 display / non-display 】

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Academic Awards Received 【 display / non-display 】

  • Young Investigator Award

    2017.10   The Japan Society of Diabetic Complications   Transcriptional and epigenetic regulation in adipocytes and its significance in glucose, lipid and energy homeostasis

    Winner： Hironori Waki

  • Society Award

    2017.09   The Japanese Constitutional Medicine   Transcriptional and epigenetic regulation in adipocytes and its significance in life-style diseases

    Winner： Hironori Waki

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Grant-in-Aid for Scientific Research 【 display / non-display 】

  • Epigenetic Regulation of Adipocyte Progenitor Cells

    Grant-in-Aid for Challenging Research (Exploratory)

    Project Year： 2021.07  -  2023.03 

  • Epigenetic Regulation of Adipocyte Progenitor Cells

    Grant-in-Aid for Challenging Research (Exploratory)

    Project Year： 2021.07  -  2023.03 

  • Epigenetic Regulation of Adipocyte Progenitor Cells

    Grant-in-Aid for Challenging Research (Exploratory)

    Project Year： 2021.07  -  2023.03 

  • Epigenetic Regulation of Adipocyte Progenitor Cells

    Grant-in-Aid for Challenging Research (Exploratory)

    Project Year： 2021.07  -  2023.03 

  • Epigenetic Regulation of Adipocyte Progenitor Cells

    Grant-in-Aid for Challenging Research (Exploratory)

    Project Year： 2021.07  -  2023.03 

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Presentations 【 display / non-display 】

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Academic Activity 【 display / non-display 】

  • Japan Association for Diabetes Education and Care

    2024.04
    -
    Now

    Deligate

  • Akita Univeristy Hospital

    2024.04
    -
    Now

    Deputy Hospital Director

  • Japan Society for the Study of Obesity

    2024.03
    -
    Now

    Education Committee Members

  • The Japan Society for the Study of Obesity

    2024.03
    -
    Now

    Auditor

  • Japan Society for the Study of Obesity

    2024.03
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    Now

    Chair of Young Committee

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Lifelong learning support results 【 display / non-display 】

  • The University of Tokyo Hospital, diabetes patient advocacy group "Kakehashi"

    Department of Diabetes and Metabolic Diseases, the University of Tokyo Hospital 

    2009.02
    -
    2021.05

  • The University of Tokyo Hospital, type 1 and mitochondrial diabetes patient advocacy group "Himawari"

    Department of Diabetes and Metabolic Diseases, the University of Tokyo Hospital 

    2009.02
    -
    2021.05

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Media Report 【 display / non-display 】

  • Prevention of complications of diabetes

    First Saturday of each month: from 17:25 to 17:30 Akita Broadcasting System (ABS) First Sunday of each month: from 17:25 to 17:30 Akita Asahi Broadcasting (AAB) Second Saturday of each month: from 13:55 to 14:00 Akita Television (AKT)

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