研究者業績

山崎 未来

Yamazaki Mirai

基本情報

所属
藤田医科大学 医学部 医学科 衛生学 講師
学位
博士(医療科学)

J-GLOBAL ID
201901005807798674
researchmap会員ID
B000354107

論文

 49
  • Mirai Yamazaki, Hiroya Yamada, Eiji Munetsuna, Yoshitaka Ando, Genki Mizuno, Atsushi Teshigawara, Hayato Ichikawa, Yuki Nouchi, Itsuki Kageyama, Takuya Wakasugi, Hiroaki Ishikawa, Nobutaka Ohgami, Koji Suzuki, Koji Ohashi
    The Journal of nutritional biochemistry 131 109671-109671 2024年5月18日  査読有り筆頭著者責任著者
    Nutritional researches have successfully used animal models to gain new insights into nutrient action. However, comprehensive descriptions of their molecular mechanisms of action remain elusive as appropriate in vitro evaluation systems are lacking. Organoid models can mimic physiological structures and reproduce in vivo functions, making them increasingly utilized in biomedical research for a better understand physiological and pathological phenomena. Therefore, organoid modeling can be a powerful approach for to understand the molecular mechanisms of nutrient action. The present study aims to demonstrate the utility of organoids in nutritional research by further investigating the molecular mechanisms responsible for the negative effects of fructose intake using liver organoids. Here, we treated liver organoids with fructose and analyzed their gene expression profiles and DNA methylation levels. Microarray analysis demonstrated that fructose-treated organoids exhibited increased selenoprotein p (Sepp1) gene expression, whereas pyrosequencing assays revealed reduced DNA methylation levels in the Sepp1 region. These results were consistent with observations using hepatic tissues from fructose-fed rats. Conversely, no differences in Sepp1 mRNA and DNA methylation levels were observed in two-dimensional cells. These results suggest that organoids serve as an ideal in vitro model to recapitulate in vivo tissue responses and help to validate the molecular mechanisms of nutrient action compared to conventional cellular models.
  • Keisuke Maeda, Ryosuke Fujii, Hiroya Yamada, Eiji Munetsuna, Mirai Yamazaki, Yoshitaka Ando, Genki Mizuno, Hiroaki Ishikawa, Koji Ohashi, Yoshiki Tsuboi, Yuji Hattori, Yuya Ishihara, Nobuyuki Hamajima, Shuji Hashimoto, Koji Suzuki
    Endocrine journal 2024年3月28日  査読有り
    Thioredoxin-interacting protein (TXNIP) plays an important role in glucose metabolism, and its expression is regulated by DNA methylation (DNAm). Although the association between TXNIP DNAm and type 2 diabetes mellitus has been demonstrated in studies with a cross-sectional design, prospective studies are needed. We therefore examined the association between TXNIP DNAm levels and longitudinal changes in glycemic traits by conducting a longitudinal study involving 169 subjects who underwent two health checkups in 2015 and 2019. We used a pyrosequencing assay to determine TXNIP DNAm levels in leukocytes (cg19693031). Logistic regression analyses were performed to assess the associations between dichotomized TXNIP DNAm levels and marked increases in glycemic traits. At four years, the TXNIP DNA hypomethylation group had a higher percentage of changes in fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) compared to those in the hypermethylation group. The adjusted odds ratios for FPG and HbA1c levels were significantly higher in the TXNIP DNA hypomethylation group than in the hypermethylation group. We found that TXNIP DNA hypomethylation at baseline was associated with a marked increase in glycemic traits. Leukocyte TXNIP DNAm status could potentially be used as an early biomarker for impaired glucose homeostasis.
  • Yoshitaka Ando, Eiji Munetsuna, Hiroya Yamada, Miyuki Ikeya, Atsushi Teshigawara, Itsuki Kageyama, Yuki Nouchi, Takuya Wakasugi, Mirai Yamazaki, Genki Mizuno, Yoshiki Tsuboi, Hiroaki Ishikawa, Nobutaka Ohgami, Koji Suzuki, Koji Ohashi
    Life sciences 336 122315-122315 2024年1月1日  査読有り
    AIMS: The developmental origin of health and disease (DOHaD) theory postulates that poor nutrition during fetal life increases the risk of disease later in life. Excessive fructose intake has been associated with obesity, diabetes, and nonalcoholic fatty liver disease, and maternal fructose intake during pregnancy has been shown to affect offspring health. In this study, we investigated the effects of high maternal fructose intake on the liver stem/progenitor cells of offspring. MAIN METHOD: A fructose-based DOHaD model was established using Sprague-Dawley rats. Small hepatocytes (SHs), which play an important role in liver development and regeneration, were isolated from the offspring of dams that were fed a high-fructose corn syrup (HFCS) diet. The gene expression and DNA methylation patterns were analyzed on postnatal day (PD) 21 and 60. KEY FINDINGS: Maternal HFCS intake did not affect body weight or caloric intake, but differences in gene expression and DNA methylation patterns were observed in the SHs of offspring. Functional analysis revealed an association between metabolic processes and ion transport. SIGNIFICANCE: These results suggest that maternal fructose intake affects DNA methylation and gene expression in the liver stem/progenitor cells of offspring. Furthermore, the prolonged retention of these changes in gene expression and DNA methylation in adulthood (PD 60) suggests that maternal fructose intake may exert lifelong effects. These findings provide insights into the DOHaD for liver-related disorders and highlight the importance of maternal nutrition for the health of the next generation.
  • Genki Mizuno, Hiroya Yamada, Yoshiki Tsuboi, Eiji Munetsuna, Mirai Yamazaki, Yoshitaka Ando, Itsuki Kageyama, Yuki Nouchi, Atsushi Teshigawara, Yuji Hattori, Ryosuke Fujii, Hiroaki Ishikawa, Shuji Hashimoto, Koji Ohashi, Nobuyuki Hamajima, Koji Suzuki
    The journal of nutrition, health & aging 28(1) 100013-100013 2024年1月  査読有り
    OBJECTIVES: The mitochondrial DNA (mtDNA) is unique and circular with multiple copies of the genome. The lower mtDNA copy number (mtDNA-CN) in leukocytes is associated with the risk of all-cause mortality. However, its long-term association is unknown. Thus, the study examined the association between mtDNA-CN and the risk of all-cause mortality in a long-term follow-up study in the Japanese population. DESIGN: This longitudinal study included the study cohort from an annual, population-based health checkup in the town of Yakumo, Hokkaido, Japan. SETTING AND PARTICIPANTS: 814 participants (baseline age range: 38-80 years, mean: 56.3 years) were included in this study in 1990. They were followed-up regarding mortality for about 30 years (median: 28.1 years) till 2019. MEASURES: The genomic DNA was extracted from peripheral blood mononuclear cells and the mtDNA-CN was measured using real-time polymerase chain reaction. The level of the mtDNA-CN was divided into tertiles (low, middle, and high). The participants were categorized based on their age into middle-aged (<60 years old) or old-aged (≥60 years old). Survival analysis was performed for tertile of mtDNA-CN and compared using the log-rank test. Univariate and multivariable Cox proportional hazard regression analyses were performed to assess the association between mtDNA-CN and all-cause mortality. The model adjusted with age, sex, body mass index, systolic blood pressure, smoking habit, alcohol consumption, exercise habit, and education level. RESULTS: The low levels of mtDNA-CN resulted in a significant decrease in cumulative survival rate (P <  0.05). The risk of mortality was significantly higher in the middle-aged cohort when mtDNA-CN levels were low (hazard ratios [95% confidence intervals]: 1.98 [1.10-3.56]). CONCLUSION: This study demonstrated that leukocyte mtDNA-CN is associated with future mortality risk. Our study findings may lead to further research on the early prediction of mortality and its underlying mechanisms.
  • Keisuke Maeda, Hiroya Yamada, Eiji Munetsuna, Ryosuke Fujii, Mirai Yamazaki, Yoshitaka Ando, Genki Mizuno, Yoshiki Tsuboi, Hiroaki Ishikawa, Koji Ohashi, Shuji Hashimoto, Nobuyuki Hamajima, Koji Suzuki
    International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition 2023年9月22日  査読有り
    Background: Carotenoids have been reported to exert protective effects against age-related diseases via changes in DNA methylation. Although lower thioredoxin-interacting protein (TXNIP) DNA methylation is associated with age-related diseases, only a few studies have investigated the factors influencing TXNIP DNA methylation. Carotenoids may be a factor linking TXNIP to specific pathophysiological functions. The aim of this study was to examine whether serum carotenoid levels are associated with TXNIP DNA methylation levels. Methods: We conducted a cross-sectional study using 376 health examination participants (169 men). DNA methylation levels were determined using a pyrosequencing assay. Serum carotenoid levels were determined by high-performance liquid chromatography. Multivariable regression analyses were performed to examine the associations between TXNIP DNA methylation levels and serum carotenoid levels with adjustment for age, BMI, HbA1c, CRP, smoking habits, alcohol consumption, exercise habits, and percentage of neutrophils. Results: Multiple linear regression analyses showed that TXNIP DNA methylation levels were positively associated with serum levels of zeaxanthin/lutein (β [95%CI]: 1.935 [0.184, 3.685]), β-cryptoxanthin (1.447 [0.324, 2.570]), α-carotene (1.061 [0.044, 2.077]), β-carotene (1.272 [0.319, 2.226]), total carotenes (1.255 [0.040, 2.469]), total xanthophylls (2.133 [0.315, 3.951]), provitamin A (1.460 [0.402, 2.519]), and total carotenoids (1.972 [0.261, 3.683]) in men (all p<0.05). Of these, provitamin A showed the stronger association (standardized β=0.216). No significant association of TXNIP DNA methylation and serum carotenoid was observed in women. Conclusions: The findings of this study suggest that carotenoid intake may protect against age-related diseases by altering TXNIP DNA methylation status in men.

書籍等出版物

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講演・口頭発表等

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担当経験のある科目(授業)

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共同研究・競争的資金等の研究課題

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