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大学院医学系研究科（医学専攻等） 医学専攻 病態制御医学系 代謝・内分泌内科学講座 |
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研究室住所 |
秋田市本道一丁目1の1 |
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研究室電話 |
018-884-6769 |
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メールアドレス |
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脇 裕典 (ワキ ヒロノリ)
WAKI Hironori
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職務経歴（学外） 【 表示 ／ 非表示 】
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2019年09月-2021年05月
東京大学大学院医学系研究科代謝・栄養病態学 准教授
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2018年11月-2019年08月
東京大学大学院医学系研究科代謝・栄養病態学 講師
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2016年09月-2018年10月
東京大学大学院医学系研究科分子糖尿病科学 特任准教授
研究分野 【 表示 ／ 非表示 】
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ライフサイエンス / 代謝、内分泌学 / Diabetes and Metabolic Diseases
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ライフサイエンス / 遺伝学 / Genomics
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ライフサイエンス / 分子生物学 / Molecular biology
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ライフサイエンス / 栄養学、健康科学
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ライフサイエンス / 細胞生物学 / Cellular biology
研究等業績 【 表示 ／ 非表示 】
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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年08月
研究論文（学術雑誌）
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年04月
研究論文（学術雑誌）
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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Beiging of perivascular adipose tissue regulates its inflammation and vascular remodeling.
Yusuke Adachi, Kazutaka Ueda, Seitaro Nomura, Kaoru Ito, Manami Katoh, Mikako Katagiri, Shintaro Yamada, Masaki Hashimoto, Bowen Zhai, Genri Numata, Akira Otani, Munetoshi Hinata, Yuta Hiraike, Hironori Waki, Norifumi Takeda, Hiroyuki Morita, Tetsuo Ushiku, Toshimasa Yamauchi, Eiki Takimoto, Issei Komuro
Nature communications 13 ( 1 ) 5117 - 5117 2022年09月 [査読有り]
研究論文（学術雑誌）
Although inflammation plays critical roles in the development of atherosclerosis, its regulatory mechanisms remain incompletely understood. Perivascular adipose tissue (PVAT) has been reported to undergo inflammatory changes in response to vascular injury. Here, we show that vascular injury induces the beiging (brown adipose tissue-like phenotype change) of PVAT, which fine-tunes inflammatory response and thus vascular remodeling as a protective mechanism. In a mouse model of endovascular injury, macrophages accumulate in PVAT, causing beiging phenotype change. Inhibition of PVAT beiging by genetically silencing PRDM16, a key regulator to beiging, exacerbates inflammation and vascular remodeling following injury. Conversely, activation of PVAT beiging attenuates inflammation and pathological vascular remodeling. Single-cell RNA sequencing reveals that beige adipocytes abundantly express neuregulin 4 (Nrg4) which critically regulate alternative macrophage activation. Importantly, significant beiging is observed in the diseased aortic PVAT in patients with acute aortic dissection. Taken together, vascular injury induces the beiging of adjacent PVAT with macrophage accumulation, where NRG4 secreted from the beige PVAT facilitates alternative activation of macrophages, leading to the resolution of vascular inflammation. Our study demonstrates the pivotal roles of PVAT in vascular inflammation and remodeling and will open a new avenue for treating atherosclerosis.
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Yuta Hiraike, Shuichi Tsutsumi, Takahito Wada, Misato Oguchi, Kaede Saito, Masahiro Nakamura, Satoshi Ota, Michinori Koebis, Harumi Nakao, Atsu Aiba, Gaku Nagano, Haruya Ohno, Kenji Oki, Masayasu Yoneda, Takashi Kadowaki, Hiroyuki Aburatani, Hironori Waki, Toshimasa Yamauchi
iScience ( Elsevier BV ) 25 ( 8 ) 104729 - 104729 2022年08月 [査読有り]
研究論文（学術雑誌）
Thermogenic brown and beige adipocytes counteract obesity by enhancing energy dissipation via uncoupling protein-1 (Ucp1). However, the effect of genetic variation on these cells, a major source of disease susceptibility, has been less well studied. Here we examined beige adipocytes from obesity-prone C57BL/6J (B6) and obesity-resistant 129X1/SvJ (129) mouse strains and identified a cis-regulatory variant rs47238345 that is responsible for differential Ucp1 expression. The alternative T allele of rs47238345 at the Ucp1 -12kb enhancer in 129 facilitates the allele-specific binding of nuclear factor I-A (NFIA) to mediate allele-specific enhancer-promoter interaction and Ucp1 transcription. Furthermore, CRISPR-Cas9/Cpf1-mediated single nucleotide polymorphism (SNP) editing of rs47238345 resulted in increased Ucp1 expression. We also identified Lim homeobox protein 8 (Lhx8), whose expression is higher in 129 than in B6, as a trans-acting regulator of Ucp1 in mice and humans. These results demonstrate the cis- and trans-acting effects of genetic variation on Ucp1 expression that underlie phenotypic diversity.
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A Pilot Study to Assess Glucose, Insulin, and Incretin Responses Following Novel High Resistant Starch Rice Ingestion in Healthy Men.
Kazuyuki Takahashi, Hiroki Fujita, Naoko Fujita, Yuya Takahashi, Shunsuke Kato, Tatsunori Shimizu, Yumi Suganuma, Takehiro Sato, Hironori Waki, Yuichiro Yamada
Diabetes therapy : research, treatment and education of diabetes and related disorders 13 ( 7 ) 1383 - 1393 2022年07月 [査読有り]
研究論文（学術雑誌）
INTRODUCTION: A newly developed resistant starch (RS) rice line with double mutation of starch synthase IIIa and branching enzyme IIb (ss3a/be2b) exhibits a tenfold greater percentage RS value than the wild-type rice line. Currently, the effects of cooked rice with such high RS content on secretion and action of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are unclear. Therefore, we conducted a pilot study to assess postprandial responses of GLP-1 and GIP along with glucose and insulin and also gastric emptying after ingestion of the high-RS cooked rice with ss3a/be2b in healthy subjects. METHODS: In a non-randomized crossover design, five healthy men ingested two test foods, control (low-RS) and high-RS cooked rice, with at least 1-week washout period between testing days. Plasma glucose, serum insulin, plasma total GLP-1, plasma total GIP, and also gastric emptying rate were measured after ingestion of each test food, and the incremental area under the curves (iAUC) was calculated for each biochemical parameter using the values from 0 to 180 min after ingestion. RESULTS: The high-RS cooked rice ingestion tended to reduce iAUC-glucose (p = 0.06) and significantly reduced iAUC-insulin (p < 0.01) and iAUC-GLP-1 (p < 0.05) but not iAUC-GIP (p = 0.21) relative to control cooked rice ingestion. In addition, the high-RS cooked rice ingestion did not affect gastric emptying. CONCLUSIONS: The present results indicate that the suppressive effects of the high-RS cooked rice ingestion on postprandial responses of glucose and insulin may be provided through attenuation in GLP-1 secretion along with its low digestibility into glucose. We suggest that the high-RS rice with ss3a/be2b may serve as a better carbohydrate source and also as a novel functional food for dietary interventions to improve postprandial hyperglycemia and hyperinsulinemia without both enhancing GLP-1 secretion and affecting gastric emptying in patients with diabetes.
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脂肪細胞の最新科学
脇 裕典
Medical View Point ( 医事出版社 ) 44 ( 9 ) 6 - 6 2023年09月
総説・解説（商業誌）
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安藤清香, 脇裕典
診断と治療 ( (株)診断と治療社 ) 110 ( 10 ) 1281 - 1285 2022年10月
総説・解説（学術雑誌）
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高血糖と肥満の深い関係ー血糖値がなかなか下がらないときは過体重への対応が必要？
脇 裕典
月間糖尿病ライフ さかえ ( 日本糖尿病協会 ) 62 ( 9 ) 12 - 13 2022年09月
総説・解説（学術雑誌）
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田丸 新一, 諏訪内 浩紹, 小田原 雅人, 鈴木 亮, 脇 裕典, 山内 敏正
東京医科大学雑誌 ( 東京医科大学医学会 ) 80 ( 2 ) 158 - 158 2022年04月
研究論文（大学，研究機関紀要）
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遠隔診療支援システムに向けたCNN-SVMによる爪白癬分類
三浦 翔流, 鄒 敏, 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 ( 一般社団法人 産業応用工学会 ) 2023 ( 0 ) 23 - 24 2023年
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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特集 心血管病の治療薬・予防薬の進歩:最新薬物治療のエッセンス 薬物療法のエッセンス 病態別・疾患別の使いかた 2型糖尿病の薬物治療
安藤 清香, 脇 裕典
診断と治療 ( (株)診断と治療社 ) 110 ( 10 ) 1281 - 1285 2022年10月
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強化インスリン療法からGLP-1受容体作動薬週1回製剤に変更して血糖コントロールが改善した高齢者2型糖尿病の1例
高橋 侑也, 藤田 浩樹, 外山 はな子, 高橋 和之, 加藤 俊祐, 安藤 清香, 山田 芙久子, 清水 辰徳, 脇 裕典
日本老年医学会雑誌 ( (一社)日本老年医学会 ) 59 ( 4 ) 573 - 573 2022年10月
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著しい高血糖による不安定型HbA1cの増加でHbA1cが測定不能であった劇症1型糖尿病と2型糖尿病の2症例
大高 いずみ, 外山 はな子, 楠見 僚太, 高橋 和之, 加藤 俊祐, 奈良 光彦, 菅沼 由美, 佐藤 雄大, 森井 宰, 藤田 浩樹, 脇 裕典
糖尿病 ( (一社)日本糖尿病学会 ) 65 ( Suppl.1 ) S - 229 2022年04月
◆原著論文【 表示 ／ 非表示 】
◆総説・解説【 表示 ／ 非表示 】
◆⼤学，研究機関紀要【 表示 ／ 非表示 】
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Book（書籍） 【 表示 ／ 非表示 】
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糖尿病学2023
脇裕典, 平池勇雄, 山内敏正 ( 担当： 共著 )
診断と治療社 2023年05月 ISBN: 9784787825933
学術書
学術関係受賞 【 表示 ／ 非表示 】
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Young Investigator Award
2017年10月 日本糖尿病合併症学会 脂肪細胞における転写・エピゲノム制御と糖・脂質・エネルギー代謝における意義
受賞者： 脇 裕典 -
研究奨励賞
2017年09月 日本体質医学会 脂肪細胞における転写・エピゲノム制御と生活習慣病における意義
受賞者： 脇 裕典
科研費（文科省・学振）獲得実績 【 表示 ／ 非表示 】
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新規脂肪前駆細胞群のエピジェネティック制御機構の解明
挑戦的研究(萌芽)
研究期間: 2021年07月 - 2023年03月 代表者: 脇 裕典
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NFIAによる糖・脂質・エネルギー代謝制御の統合的理解と肥満症の治療戦略
基盤研究(B)
研究期間: 2020年04月 - 2024年03月 代表者: 脇 裕典
学会等発表 【 表示 ／ 非表示 】
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スティグマに配慮したコミュニケーションのとり方
脇 裕典 [招待有り]
第23回秋田県糖尿病療養指導研究会 特別講演 2023年09月 - 2023年09月
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２型糖尿病と肥満症の最近のトピックス
脇 裕典 [招待有り]
第18回中通医療連携セミナー 2023年07月 - 2023年07月
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Recent Topics on Obesity and Obesity-related Health Disorders
Hironori Waki
IDF-WPR Congress 2023 & 15th Scientific Meeting of AASD 2023年07月 - 2023年07月
学会・委員会等活動 【 表示 ／ 非表示 】
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日本糖尿病学会
2022年05月-継続中英文誌編集委員会, Diabetology International, associate editor
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特定非営利活動法人 秋田県糖尿病対策推進協議会
2022年05月-継続中理事長
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日本内分泌学会
2022年04月-継続中Endocrine Journal, editorial board
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日本内科学会
2022年04月-継続中評議員
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Korean Society for Biochemistry and Molecular Biology / BMB Reports
2021年03月-継続中Honorary editor
学外の社会活動（高大・地域連携等） 【 表示 ／ 非表示 】
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東京大学医学部附属病院 患者会かけはしの会（東京都糖尿病協会所属）会長
東京大学医学部附属病院 糖尿病・代謝内科
2009年02月-2021年05月 -
東京大学医学部附属病院 患者会ひまわりの会（１型糖尿病・ミトコンドリア糖尿病）会長
東京大学医学部附属病院 糖尿病・代謝内科
2009年02月-2021年05月