研究者基本情報

• 博士 (生物資源科学), 日本大学

• https://researchmap.jp/knakata_19

• https://jglobal.jst.go.jp/detail?JGLOBAL_ID=201901010056711695

• 20849244

• 201901010056711695

• 食事由来脂質
• 腸管上皮細胞

• ライフサイエンス, 消化器内科学

研究活動情報

• 2023年04月, 国立高度専門医療研究センター 医療研究連携推進本部, 理事長賞
  食事由来脂質クオリティが腸管腫瘍リスクに及ぼす影響
  中田一彰
• 2014年09月, The joint Meeting of the XVIII International Symposium on Gnotobiology (XVIII-ISG) and III International Ecological Forum “Environmental and human health” (EcoForum), マリー・E・コーツ賞（第18回ノトバイオロジー国際シンポジウム 若手研究者 最優秀ポスター賞
  The commensal bacteria and short chain fatty acids affect to immunoglobulin A production by the immune cells derived from the gut associated lymphoid tissues in small and large intestines
  Kazuaki Nakata

• Identification and characterization of CXCL13 producers in bone tissue in response to fasting.
  Takuma Okawa; Motoyoshi Nagai; Shinya Fujita; Koichiro Suzuki; Kazuaki Nakata; Reina Miyajima; Hiroaki Shiratori; Seiga Komiyama; Daisuke Takahashi; Yuki I Kawamura; Taeko Dohi; Burkhard Ludewig; Keiyo Takubo; Koji Hase
  International immunology, 2026年01月30日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The bone tissue serves as a dynamic reservoir that accommodates diverse immune cell populations during low-energy states such as fasting. Energy-restriction and reduced metabolism induce a transient migration of naïve B cells from Peyer's patches to the bone marrow in mice, a process driven by the upregulation of Cxcl13 expression within the bone niche. However, the specific cellular source of CXCL13 and the upstream signals regulating its expression remain undefined. Our analysis identified the lineage-negative fraction of the bone as the major source of CXCL13. Single-cell RNA sequencing of these cells further demonstrated that Cxcl13 was selectively expressed by osteogenic mesenchymal stromal cells (MSCs) during fasting. Consistently, immunofluorescence imaging showed an increased frequency of these CXCL13-producing cells under fasting conditions, primarily localized within the perivascular niche. Gene ontology analysis of differentially expressed genes in these cells during fasting revealed enrichment of TGF-β and PPAR signaling. In line with this, pharmacological intervention in either the TGF-β or PPARγ signaling pathway significantly attenuated fasting-induced naïve B-cell migration and CXCL13 production in the bone. These results establish a mechanistic link between systemic metabolic cues and the bone marrow immune microenvironment. We propose that osteogenic MSCs play a vital role in orchestrating this trafficking program for naïve B cells, underscoring a dynamic crosstalk between the bone stromal cells and the immune system.
• Dietary stearic acid accelerates intestinal tumorigenesis via fatty acid-binding protein 5 without promoting obesity.
  Kazuaki Nakata; Seiga Komiyama; Keisuke Sekine; Motoyoshi Nagai; Takuma Okawa; Wakana Ohashi; Kenta Nakano; Tadashi Okamura; Takuma Kozono; Nobuyuki Takemura; Kazuhiko Yamada; Norihiro Kokudo; Taeko Dohi; Koji Hase; Yuki I Kawamura
  Cellular and molecular gastroenterology and hepatology, 101740, 101740, 2026年01月28日, ［査読有り］, ［筆頭著者］, ［国際誌］
  英語, 研究論文（学術雑誌）, BACKGROUND & AIMS: Dietary fat increases the risk of intestinal cancer, but the effect of the fatty acid composition on tumorigenesis is unclear. The aim of this study is to investigate the impact of diets with different fatty acids on carcinogenesis in the intestine. METHODS: Mice were fed a linoleic acid (LA)-rich or stearic acid (SA)-rich high-fat diet (HFD) from the age of 4 weeks. The ApcMin/+ mice and an azoxymethane- and a dextran sulfate sodium-induced colorectal cancer (CRC) mouse model were used to examine the effects of different dietary fatty acids on CRC development. fatty acid-binding protein 5 (FABP5) knockout mice and SBFI-26, an inhibitor of FABP5, were used to assess its contribution. RESULTS: We found that an SA-rich HFD more strongly accelerated tumorigenesis in murine CRC models than an LA-rich HFD, with fewer obesity phenotypes compared with LA-rich HFD-fed mice. Dietary SA more strongly promoted epithelial cell proliferation and Paneth cell differentiation than LA, whereas no differences in the numbers of leucine-rich repeat-containing G protein-coupled receptor 5+ and B lymphoma Mo-MLV insertion region 1 homolog+ intestinal stem cells were detected between the groups. In murine and human intestinal organoids, SA promoted crypt formation. We found that FABP5 was expressed in a small population of Ki67+ proliferative cells in crypts, and the number of Ki67+ FABP5+ cells was increased by SA-rich HFD feeding. FABP5 inhibition suppressed SA-induced epithelial cell proliferation, Paneth cell differentiation, and tumorigenesis. CONCLUSIONS: Dietary SA can promote CRC via FABP5 without promoting obesity.
• Intervention in gut microbiota increases intestinal γ-aminobutyric acid and alleviates anxiety behavior: a possible mechanism via the action on intestinal epithelial cells.
  Mion Ikegami; Hikari Narabayashi; Kazuaki Nakata; Miyu Yamashita; Yutaka Sugi; Yushiro Fuji; Hiroshi Matsufuji; Gaku Harata; Kazutoyo Yoda; Kenji Miyazawa; Yusuke Nakanishi; Kyoko Takahashi
  Frontiers in cellular and infection microbiology, 14, 1421791, 1421791, Frontiers Media SA, 2024年09月05日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The role of the gut microbiota in the gut-brain axis has attracted attention in recent years. Some gut microbiota produces γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in mammals, in vitro, but the correlation between gut microbiota composition and intestinal GABA concentration, as well as the action of intestinal GABA in vivo, are poorly understood. Herein, we found that the intestinal GABA concentration was increased in mice by the intervention of the gut microbiota with neomycin or Bifidobacterium bifidum TMC3115 (TMC3115). Administration of TMC3115 reduced anxiety without affecting serum levels of serotonin, corticosterone, or GABA. We further found that intestinal epithelial cells expressed GABA receptor subunits and mediated mitogen-activated protein kinase signaling upon GABA stimulation. In addition, administration of TMC3115 induced mitogen-activated protein kinase signaling in colonic epithelial cells but not in small intestinal epithelial cells in mice. These results indicate that GABA produced by the gut microbiota, mainly in the colon, may affect host behavioral characteristics via GABA receptors expressed in intestinal epithelial cells without being transferred to the blood. This study suggests a novel mechanism by which intestinal GABA exerts physiological effects, even in the presence of the blood-brain barrier.
• Sugar and arginine facilitate oral tolerance by ensuring the functionality of tolerogenic immune cell subsets in the intestine.
  Motoyoshi Nagai; Takuma Okawa; Kazuaki Nakata; Daisuke Takahashi; Reina Miyajima; Hiroaki Shiratori; Daisuke Yamanaka; Atsuo Nakamura; Chinatsu Oyama; Shin-Ichiro Takahashi; Noriko Toyama-Sorimachi; Koichiro Suzuki; Wakana Ohashi; Taeko Dohi; Yuki I Kawamura; Koji Hase
  Cell reports, 43, 7, 114490, 114490, 2024年07月23日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Although oral tolerance is a critical system in regulating allergic disorders, the mechanisms by which dietary factors regulate the induction and maintenance of oral tolerance remain unclear. To address this, we explored the differentiation and function of various immune cells in the intestinal immune system under fasting and ad libitum-fed conditions before oral ovalbumin (OVA) administration. Fasting mitigated OVA-specific Treg expansion, which is essential for oral tolerance induction. This abnormality mainly resulted from functional defects in the CX3CR1+ cells responsible for the uptake of luminal OVA and reduction of tolerogenic CD103+ dendritic cells. Eventually, fasting impaired the preventive effect of oral OVA administration on asthma and allergic rhinitis development. Specific food ingredients, namely carbohydrates and arginine, were indispensable for oral tolerance induction by activating glycolysis and mTOR signaling. Overall, prior food intake and nutritional signals are critical for maintaining immune homeostasis by inducing tolerance to ingested food antigens.
• Purified diet affects intestinal epithelial proliferation and barrier functions through gut microbial alterations.
  Hiroaki Shiratori; Kisara M Hattori; Kazuaki Nakata; Takuma Okawa; Seiga Komiyama; Yusuke Kinashi; Yuma Kabumoto; Yuria Kaneko; Motoyoshi Nagai; Tomoko Shindo; Nobuko Moritoki; Yuki I Kawamura; Taeko Dohi; Daisuke Takahashi; Shunsuke Kimura; Koji Hase
  International immunology, 2024年01月23日, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, The gut microbiota plays a crucial role in maintaining epithelial barrier function. Although multiple studies have demonstrated the significance of dietary factors on gut microbiota and mucosal barrier function, the impact of a purified diet, which has long been used in various animal experiments, on intestinal homeostasis remains to be elucidated. Here, we compared the impact of two different types of diets, a crude diet and an AIN-93G-formula purified diet, on epithelial integrity and the gut microbiota. Purified diet-fed mice exhibited shorter villi and crypt lengths and slower epithelial turnover, particularly in the ileum. In addition, antimicrobial products, including islet-derived protein 3γ (REG3γ), were substantially decreased in purified diet-fed mice. Purified diet feeding also suppressed α1,2-fucosylation on the epithelial surface. Furthermore, purified diet induced metabolic rewiring to fatty acid oxidation and ketogenesis. 16S ribosomal RNA gene sequencing of the ileal contents and mucus layer revealed distinct gut microbiota compositions between the purified and crude diet-fed mice. Purified diet feeding reduced the abundance of segmented filamentous bacteria (SFB), which potently upregulate REG3γ and fucosyltransferase 2 (Fut2) by stimulating group 3 innate lymphoid cells (ILC3) to produce IL-22. These observations illustrate that the intake of a crude diet secures epithelial barrier function by facilitating SFB colonization, whereas a purified diet insufficiently establishes the epithelial barrier, at least partly owing to the loss of SFB. Our data suggest that the influence of purified diets on the epithelial barrier integrity should be considered in experiments using purified diets.
• Gut microbiota-dependent adaptor molecule recruits DNA methyltransferase to the TLR4 gene in colonic epithelial cells to suppress inflammatory reactions.
  Hikari Narabayashi; Chiharu Koma; Kazuaki Nakata; Mion Ikegami; Yusuke Nakanishi; Jun Ogihara; Masato Tsuda; Akira Hosono; Shigemasa Hanazawa; Kyoko Takahashi
  Frontiers in molecular biosciences, 9, 1005136, 1005136, 2022年, ［査読有り］, ［国際誌］
  研究論文（学術雑誌）, The intestine is inhabited by a large number of commensal bacteria that are immunologically non-self, potentially causing inflammation. However, in a healthy intestine, inflammation is strictly controlled at low levels to maintain homeostasis. We previously reported that the gut microbiota induce DNA methylation of the gene encoding Toll-like receptor (TLR) 4, a pattern recognition receptor that recognizes lipopolysaccharides of gram-negative bacteria, in colonic epithelial cells, suggesting its role in controlling intestinal inflammation. However, there remains a question of how gut microbiota cause methylation of only specific genes including TLR4, despite the fact that DNA methyltransferase (DNMT) is common to all genes targeted for methylation. Here, we identified RBM14 as an adaptor molecule that recruits DNMT to the TLR4 gene. RBM14 was shown to bind DNMT3 and be expressed at significantly higher levels in an intestinal epithelial cell (IEC) line with hypermethylated TLR4 gene than in an IEC line with hypomethylated TLR4 gene. In addition, RBM14 interacted with DNA regions of the TLR4 gene, and knockdown of RBM14 suppressed DNA methylation of the TLR4 gene in IECs. Furthermore, RBM14 expression was higher in colonic epithelial cells of conventional mice than in those of germ-free mice. Collectively, these results indicate that the gut microbiota induce methylation of the TLR4 gene in colonic epithelial cells by upregulating RBM14, which can recruit DNMT3 to the gene. The regulation of adaptor molecules such as RBM14, which bind to specific target genes and recruit DNMT, can explain, at least in part, how gut microbiota contribute to the maintenance of intestinal homeostasis through epigenetic control of specific gene expression in IECs.
• Loss of GSTO2 contributes to cell growth and mitochondria function via the p38 signaling in lung squamous cell carcinoma.
  Ryusuke Sumiya; Masayoshi Terayama; Teruki Hagiwara; Kazuaki Nakata; Keigo Sekihara; Satoshi Nagasaka; Hideki Miyazaki; Toru Igari; Kazuhiko Yamada; Yuki I Kawamura
  Cancer science, 113, 1, 195, 204, 2022年01月, ［査読有り］, ［国際誌］
  英語, 研究論文（学術雑誌）, Glutathione S-transferase omega 2 (GSTO2) lacks any appreciable GST activity, but it exhibits thioltransferase activity. The significance of GSTO2 in lung function has been reported; however, the precise expression and molecular function of GSTO2 in the lungs remain unclear. In the present study, we found that GSTO2 is expressed in airway basal cells, non-ciliated, columnar Clara cells, and type II alveolar cells, which have self-renewal capacity in the lungs. Contrastingly, no GSTO2 expression was observed in 94 lung squamous cell carcinoma (LSCC) samples. When human LSCC cell lines were treated with 5-aza-2'-deoxycytidine, a DNA-methyltransferase inhibitor, GSTO2 transcription was induced, suggesting that aberrant GSTO2 hypermethylation in LSCC is the cause of its downregulation. Forced GSTO2 expression in LSCC cell lines inhibited cell growth and colony formation in vitro. In a subcutaneous xenograft model, GSTO2-transfected cells formed smaller tumors in nude mice than mock-transfected cells. Upon intravenous injection into nude mice, the incidence of liver metastasis was lower in mice injected with GSTO2-transfected cells than in those injected with mock-transfected cells. In addition, GSTO2 induction suppressed the expression of β-catenin and the oxygen consumption rate, but it did not affect the extracellular acidification rate. Furthermore, GSTO2-transfected cells displayed lower mitochondrial membrane potential than mock-transfected cells. When GSTO2-transfected cells were treated with a p38 inhibitor, β-catenin expression and mitochondrial membrane potential were recovered. Our study indicated that the loss of GSTO2 via DNA hypermethylation contributes to the growth and progression of LSCC, probably by modulating cancer metabolism via the p38/β-catenin signaling pathway.
• Commensal microbiota-induced microRNA modulates intestinal epithelial permeability through the small GTPase ARF4
  Kazuaki Nakata; Yutaka Sugi; Hikari Narabayashi; Tetsuro Kobayakawa; Yusuke Nakanishi; Masato Tsuda; Akira Hosono; Shuichi Kaminogawa; Shigemasa Hanazawa; Kyoko Takahashi
  JOURNAL OF BIOLOGICAL CHEMISTRY, 292, 37, 15426, 15433, 2017年09月, ［査読有り］, ［筆頭著者］
  英語, 研究論文（学術雑誌）
• α-Defensin 5 gene expression is regulated by gut microbial metabolites.
  Sugi Y; Takahashi K; Kurihara K; Nakano K; Kobayakawa T; Nakata K; Tsuda M; Hanazawa S; Hosono A; Kaminogawa S
  Bioscience, biotechnology, and biochemistry, 81, 2, 242, 248, 2017年02月, ［査読有り］
  英語, 研究論文（学術雑誌）
• Post-Transcriptional Regulation of Toll-Interacting Protein in the Intestinal Epithelium
  Yutaka Sugi; Kyoko Takahashi; Kenta Kurihara; Kazuaki Nakata; Hikari Narabayashi; Yuji Hamamoto; Makoto Suzuki; Masato Tsuda; Shigemasa Hanazawa; Akira Hosono; Shuichi Kaminogawa
  PLOS ONE, 11, 10, e0164858, 2016年10月, ［査読有り］
  英語, 研究論文（学術雑誌）

• 食事由来脂質による消化管発癌リスクは上皮細胞に保持される
  中田一彰
  第98回日本生化学会大会, 2025年11月04日, 口頭発表（一般）
  2025年11月03日 - 2025年11月05日
• 食事性ステアリン酸による腸管腫瘍形成の促進におけるFABP5の役割
  第84回日本癌学会学術総会, 2025年09月27日
  2025年09月25日 - 2025年09月27日
• 食事性ステアリン酸は脂肪酸結合タンパク質5型を介して腸管腫瘍形成を促進する
  中田一彰
  第83回 日本癌学会学術総会, 2024年09月20日, 口頭発表（一般）
• DIETARY STEARIC ACID PROMOTES EPITHELIAL CELL PROLIFERATION AND TUMORIGENESIS IN THE INTESTINE VIA FATTY ACID-BINDING PROTEIN 5 UNCOUPLED WITH THE OBESE PHENOTYPE
  Kazuaki Nakata
  Digestive Disease Week 2024, 2024年05月21日
  2024年05月18日 - 2024年05月21日
• 食事由来脂質クオリティが腸管腫瘍リスクに及ぼす影響
  中田一彰
  国立高度専門医療研究センター 医療研究連携推進本部 合同リトリート, 2024年04月13日
• 腸管腫瘍形成に及ぼす食事性脂肪酸の影響
  中田一彰
  第82回 日本癌学会学術総会, 2023年09月23日
  2023年09月21日 - 2023年09月23日
• 食事由来脂質クオリティが腸管腫瘍リスクに及ぼす影響
  中田一彰
  国立高度専門医療研究センター 医療研究連携推進本部 合同リトリート, 2023年04月22日
• 食餌性脂肪酸が腸上皮恒常性維持機構ならびに消化器疾患へ及ぼす影響
  中田一彰
  日本食品免疫学会 第18回学術大会, 2022年11月08日
  2022年11月08日 - 2022年11月09日
• 食餌性ステアリン酸は腸上皮細胞のターンオーバーと腫瘍形成を促進する
  中田一彰
  第81回 日本癌学会学術総会, 2022年09月30日
  2022年09月29日 - 2022年10月01日

• 2025年06月 - 現在
  日本生化学会
• 日本癌学会
• 日本免疫学会
• 日本食品免疫学会

• 腸クロム親和性細胞動態の制御機構の解析と疾患発症の意義の解明
  科学研究費助成事業
  2026年04月01日 - 2029年03月31日
  中田 一彰
  日本学術振興会, 基盤研究(C), 北海道大学, 26K10846
• 食事中脂質クオリティーが組織恒常性維持機構に及ぼす影響とその破綻の分子機構の解明
  科学研究費助成事業
  2024年04月 - 2026年03月
  中田 一彰
  日本学術振興会, 若手研究, 国立研究開発法人国立国際医療研究センター, 24K18960
• 若年時の高脂肪食摂取が上皮バリア破綻をもたらす機構と疾患発症における意義の解明
  科学研究費助成事業
  2020年04月01日 - 2024年03月31日
  中田 一彰
  近年、ライフスタイルの変化に伴う若齢時からの肥満や代謝制御異常が増加しているが、これらの要因が将来的な悪性疾患の発症リスクにどの程度関与するかの詳細は不明である。本研究では、消化管腔と体内を隔て、食事の影響を最前で受ける腸上皮に着目し、若年時からの高脂肪摂餌が腸管機能に及ぼす影響を詳細に解析するとともに、その分子メカニズム並びに悪性疾患発症リスクに及ぼす影響を明らかにすることを目的とする。これまでの研究では、高脂肪食のラードを飽和脂肪酸、または不飽和脂肪酸に置き換えた餌を作製し、これら異なる脂質が腸管に及ぼす影響を解析した結果、不飽和脂肪酸含有高脂肪食摂餌群と比較して、飽和脂肪酸含有高脂肪食摂餌群で増殖細胞が増加していることを見出した。今年度は、飽和脂肪酸の上皮細胞増殖亢進作用が、腸上皮細胞への直接作用か否かを検討するために、マウス小腸よりクリプトを単離し、ゲル中で三次元培養するオルガノイド培養系を用いたに検証を行った。オルガノイド培養系に各種脂肪酸を添加培養し、オルガノイドあたりのクリプト形成頻度を解析した結果、飽和脂肪酸添加によりクリプト数が増加したことから、飽和脂肪酸は直接上皮細胞に作用して細胞増殖を促進することが明らかになった。さらに大腸癌マウスモデルであるAPCMin/+マウスを用いて、脂質の種類の違いが疾患発症に及ぼす影響を検討した結果、不飽和脂肪酸含有高脂肪食摂餌群と比較して、飽和脂肪酸食群で腫瘍形成が促進されることが明らかになった。以上から、飽和脂肪酸による腸上皮恒常性の破綻が腫瘍形成に寄与することが明らかになった。
  日本学術振興会, 若手研究, 国立研究開発法人国立国際医療研究センター, 20K17007