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Affiliation |
Graduate School of Medicine Doctorial Course in Medicine Bioregulatory Medicine Department of Metabolism and Endocrinology |
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Mail Address |
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WAKI Hironori
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Research Interests 【 display / non-display 】
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脂肪細胞
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肥満
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Obesity
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Adipocytes
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Brown adipocytes
Graduating School 【 display / non-display 】
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-1997.03
The University of Tokyo Faculty of Medicine Graduated
Graduate School 【 display / non-display 】
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-2003.03
The University of Tokyo Graduate School, Division of Medicine Doctor's Course Completed
Campus Career 【 display / non-display 】
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2021.06-Now
Akita University Graduate School of Medicine Doctorial Course in Medicine Bioregulatory Medicine Department of Metabolism and Endocrinology Professor
External Career 【 display / non-display 】
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2019.09-2021.05
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo Associate Professor
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2018.11-2019.08
Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo Lecturer
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2016.09-2018.10
Department of Molecular Sciences on Diabetes, Graduate School of Medicine, the University of Tokyo Project Associate Professor
Research Areas 【 display / non-display 】
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Life Science / Molecular biology / Molecular biology
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Life Science / Nutrition science and health science
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Life Science / Cell biology / Cellular biology
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Life Science / Genetics / Genomics
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Life Science / Metabolism and endocrinology / Diabetes and Metabolic Diseases
Research Achievements 【 display / non-display 】
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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.
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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.
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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.
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NFIA in adipocytes reciprocally regulates mitochondrial and inflammatory gene program to improve glucose homeostasis.
Yuta Hiraike, Kaede Saito, Misato Oguchi, Takahito Wada, Gotaro Toda, Shuichi Tsutsumi, Kana Bando, Junji Sagawa, Gaku Nagano, Haruya Ohno, Naoto Kubota, Tetsuya Kubota, Hiroyuki Aburatani, Takashi Kadowaki, Hironori Waki, Shintaro Yanagimoto, Toshimasa Yamauchi
Proceedings of the National Academy of Sciences of the United States of America 120 ( 31 ) e2308750120 2023.08
Research paper (journal)
Adipose tissue is central to regulation of energy homeostasis. Adaptive thermogenesis, which relies on mitochondrial oxidative phosphorylation (Ox-Phos), dissipates energy to counteract obesity. On the other hand, chronic inflammation in adipose tissue is linked to type 2 diabetes and obesity. Here, we show that nuclear factor I-A (NFIA), a transcriptional regulator of brown and beige adipocytes, improves glucose homeostasis by upregulation of Ox-Phos and reciprocal downregulation of inflammation. Mice with transgenic expression of NFIA in adipocytes exhibited improved glucose tolerance and limited weight gain. NFIA up-regulates Ox-Phos and brown-fat-specific genes by enhancer activation that involves facilitated genomic binding of PPARγ. In contrast, NFIA in adipocytes, but not in macrophages, down-regulates proinflammatory cytokine genes to ameliorate adipose tissue inflammation. NFIA binds to regulatory region of the Ccl2 gene, which encodes proinflammatory cytokine MCP-1 (monocyte chemoattractant protein-1), to down-regulate its transcription. CCL2 expression was negatively correlated with NFIA expression in human adipose tissue. These results reveal the beneficial effect of NFIA on glucose and body weight homeostasis and also highlight previously unappreciated role of NFIA in suppressing adipose tissue inflammation.
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Relationships among Postprandial Plasma Active GLP-1 and GIP Excursions, Skeletal Muscle Mass, and Body Fat Mass in Patients with Type 2 Diabetes Treated with Either Miglitol, Sitagliptin, or Their Combination: A Secondary Analysis of the MASTER Study.
Masahiro Sato, Hiroki Fujita, Hiroki Yokoyama, Atsushi Mikada, Yohei Horikawa, Yuya Takahashi, Yuichiro Yamada, Hironori Waki, Takuma Narita
Journal of clinical medicine 12 ( 9 ) 2023.04
Research paper (journal)
BACKGROUND: We previously conducted a pilot randomized controlled trial "the MASTER study" and demonstrated that alpha-glucosidase inhibitor miglitol and a dipeptidyl peptidase-4 inhibitor sitagliptin modified postprandial plasma excursions of active glucagon-like peptide-1 (aGLP-1) and active gastric inhibitory polypeptide (aGIP), and miglitol treatment decreased body fat mass in patients with type 2 diabetes (T2D). However, the details regarding the relationships among postprandial plasma aGLP-1 and aGIP excursions, skeletal muscle mass, and body fat mass are unclear. METHODS: We conducted a secondary analysis of the relationships among skeletal muscle mass index (SMI), total body fat mass index (TBFMI), and the incremental area under the curves (iAUC) of plasma aGLP-1 and aGIP excursions following mixed meal ingestion at baseline and after 24-week add-on treatment with either miglitol alone, sitagliptin alone, or their combination in T2D patients. RESULTS: SMI was not changed after the 24-week treatment with miglitol and/or sitagliptin. TBFMI was reduced and the rates of aGIP-iAUC change were lowered in the two groups treated with miglitol, although their correlations did not reach statistical significance. We observed a positive correlation between the rates of aGIP-iAUC and TBFMI changes and a negative correlation between the rates of TBFMI and SMI changes in T2D patients treated with sitagliptin alone whose rates of aGIP-iAUC change were elevated. CONCLUSIONS: Collectively, although T2D patients treated with miglitol and/or sitagliptin did not show altered SMI after 24-week treatment, the current study suggests that there are possible interrelationships among postprandial plasma aGIP excursion modified by sitagliptin, skeletal muscle mass, and body fat mass.
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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)
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One point advice---How much is your best weight?
Hironori Waki
Medical Practice 40 ( 5 ) 800 - 800 2023.05
Introduction and explanation (scientific journal)
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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)
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Genetics in obesity and obeesity stigma
Hironori Waki
DM Ensemble ( Nikkei Medical ) 11 ( 2 ) 36 - 37 2022.08
Introduction and explanation (scientific journal)
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Hironori Waki
Japanese Journal of Clinical Medicine 80 ( 4 ) 607 - 701 2022.04
Introduction and explanation (scientific journal)
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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.
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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
◆Original paper【 display / non-display 】
◆Introduction and explanation【 display / non-display 】
◆Other【 display / non-display 】
Books 【 display / non-display 】
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Pharmacological approach to treat diabetes mellitus
Takehiro Sato, Hironori Waki
2023.11 ISBN: 9784784903740
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シリーズGノート患者さんに合わせた糖尿病治療ができる血糖管理と薬剤選択の大原則
Kazuyuki Takahashi, Hironori Waki
HYODOSHA 2022.11 ISBN: 9784758123570
Academic Awards Received 【 display / non-display 】
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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
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Society Award
2017.09 The Japanese Constitutional Medicine Transcriptional and epigenetic regulation in adipocytes and its significance in life-style diseases
Winner： Hironori Waki
Grant-in-Aid for Scientific Research 【 display / non-display 】
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Epigenetic Regulation of Adipocyte Progenitor Cells
Grant-in-Aid for Challenging Research (Exploratory)
Project Year： 2021.07 - 2023.03
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Epigenetic Regulation of Adipocyte Progenitor Cells
Grant-in-Aid for Challenging Research (Exploratory)
Project Year： 2021.07 - 2023.03
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Epigenetic Regulation of Adipocyte Progenitor Cells
Grant-in-Aid for Challenging Research (Exploratory)
Project Year： 2021.07 - 2023.03
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Epigenetic Regulation of Adipocyte Progenitor Cells
Grant-in-Aid for Challenging Research (Exploratory)
Project Year： 2021.07 - 2023.03
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Epigenetic Regulation of Adipocyte Progenitor Cells
Grant-in-Aid for Challenging Research (Exploratory)
Project Year： 2021.07 - 2023.03
Presentations 【 display / non-display 】
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Hironori Waki [Invited]
IDF congress 2023 2023.12 - 2023.12 IDF
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The epigenome of adipocytes and energy homeostasis
Hironori Waki, Tatsunori Shimizu, Misato Oguchi, Kaede Saito, Yuta Hiraike, Tomohisa Aoyama, Shuichi Tsutsumi, Kazuki Yasuda, Kazuyuki Tobe, Shintaro Narita, Tomonori Habuchi, Toshimasa Yamauchi [Invited]
The 44th Annual Meeting of Japan Society for the Study of Obesity (JASSO 44) / The 41st Annual Meeting of the Japanese Society for Treatment of Obesity (JSTO 41) 2023.11 - 2023.11
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Utilizing Information and Communication Technology for Diabetes Healthcare
Hironori Waki [Invited]
Medical Science Cafe in Senboku 2023.10 - 2023.10
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Do you know about diabetic nephropathy?
Hironori Waki
Akita University Open Lecture 2023.10 - 2023.10
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よく知って上手につきあう肥満と糖尿病 ～最近のトピックス～
Hironori Waki [Invited]
第48回地域の医療を考える集い 2023.10 - 2023.10
Academic Activity 【 display / non-display 】
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2024.04-Now
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Akita Univeristy Hospital
2024.04-NowDeputy Hospital Director
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Japan Society for the Study of Obesity
2024.03-NowEducation Committee Members
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The Japan Society for the Study of Obesity
2024.03-NowAuditor
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Japan Society for the Study of Obesity
2024.03-NowChair of Young Committee
Lifelong learning support results 【 display / non-display 】
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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