22 results on '"Nouchi Y"'
Search Results
2. Approaches to nutritional research using organoids; fructose treatment induces epigenetic changes in liver organoids.
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Yamazaki M, Yamada H, Munetsuna E, Ando Y, Mizuno G, Teshigawara A, Ichikawa H, Nouchi Y, Kageyama I, Wakasugi T, Ishikawa H, Ohgami N, Suzuki K, and Ohashi K
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- Animals, Rats, Male, Humans, Organoids drug effects, Organoids metabolism, Fructose pharmacology, Liver metabolism, Liver drug effects, DNA Methylation drug effects, Epigenesis, Genetic drug effects
- Abstract
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., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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3. Low mitochondrial DNA copy number in peripheral blood mononuclear cells is associated with future mortality risk: a long-term follow-up study from Japan.
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Mizuno G, Yamada H, Tsuboi Y, Munetsuna E, Yamazaki M, Ando Y, Kageyama I, Nouchi Y, Teshigawara A, Hattori Y, Fujii R, Ishikawa H, Hashimoto S, Ohashi K, Hamajima N, and Suzuki K
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- Humans, Middle Aged, Aged, Aged, 80 and over, Follow-Up Studies, Japan, DNA Copy Number Variations, Longitudinal Studies, DNA, Mitochondrial genetics, Leukocytes, Mononuclear
- Abstract
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., (Copyright © 2023. Published by Elsevier Masson SAS.)
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- 2024
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4. Impact of maternal fructose intake on liver stem/progenitor cells in offspring: Insights into developmental origins of health and disease.
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Ando Y, Munetsuna E, Yamada H, Ikeya M, Teshigawara A, Kageyama I, Nouchi Y, Wakasugi T, Yamazaki M, Mizuno G, Tsuboi Y, Ishikawa H, Ohgami N, Suzuki K, and Ohashi K
- Subjects
- Pregnancy, Rats, Humans, Animals, Female, Rats, Sprague-Dawley, Obesity metabolism, Liver metabolism, Fructose adverse effects, Maternal Nutritional Physiological Phenomena, Prenatal Exposure Delayed Effects metabolism, High Fructose Corn Syrup
- Abstract
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., Competing Interests: Declaration of competing interest None of the authors have any potential conflicts of interest associated with this research., (Copyright © 2023 Elsevier Inc. All rights reserved.)
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- 2024
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5. Intracellular Major Histocompatibility Complex Class II and C-X-C Motif Chemokine Ligand 10-Expressing Neutrophils Indicate the State of Anti-Tumor Activity Induced by Bacillus Calmette-Guérin .
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Takeda Y, Kato T, Sabrina S, Naito S, Ito H, Emi N, Kuboki Y, Takai Y, Fukuhara H, Ushijima M, Narisawa T, Yagi M, Kanno H, Sakurai T, Nishida H, Araki A, Shimotai Y, Nagashima M, Nouchi Y, Saitoh S, Nara H, Tsuchiya N, and Asao H
- Abstract
(1) Background: Inflammatory responses induce the formation of both anti-tumor and pro-tumor neutrophils known as myeloid-derived suppressor cells (MDSCs). Intermittent intravesical infusion of Bacillus Calmette-Guérin (BCG) is an established cancer immunotherapy for non-muscle-invasive bladder cancer (NMIBC). However, the types of neutrophils induced via the inflammatory response to both tumor-bearing and BCG remain unclear. (2) Methods: We therefore analyzed neutrophil dynamics in the peripheral blood and urine of patients with NMIBC who received BCG therapy. Further, we analyzed the effects of BCG in a mouse intraperitoneal tumor model. (3) Results: BCG therapy induced the formation of CXCL10 and MHC class II-positive neutrophils in the urine of patients with NMIBC but did not induce MDSC formation. CXCL10- and MHC class II-expressing neutrophils were detected in peritoneal exudate cells formed after BCG administration. Partial neutrophil depletion using an anti-Ly6G antibody suppressed the upregulation of CXCL10 and MHC class II in neutrophils and reversed the anti-tumor activity of BCG in mouse models. (4) Conclusions: These results indicated that intracellular MHC class II- and CXCL10-expressing neutrophils indicate the state of anti-tumor activity induced via BCG. The status of neutrophils in mixed inflammation of immunosuppressive and anti-tumor responses may therefore be useful for evaluating immunological systemic conditions.
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- 2023
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6. Laboratory analysis of glucose, fructose, and sucrose contents in Japanese common beverages for the exact assessment of beverage-derived sugar intake.
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Ando Y, Ohta Y, Munetsuna E, Yamada H, Nouchi Y, Kageyama I, Mizuno G, Yamazaki M, Fujii R, Ishikawa H, Suzuki K, Hashimoto S, and Ohashi K
- Abstract
Objectives: The adverse health effects of consuming sugar-sweetened beverages have been studied worldwide. However, no recent report on the actual sugar contents of Japanese sugar-sweetened beverages is available. Therefore, we analyzed the glucose, fructose, and sucrose contents of common Japanese beverages., Methods: The glucose, fructose, and sucrose contents of 49 beverages (8 energy drinks, 11 sodas, 4 fruit juices, 7 probiotic drinks, 4 sports drinks, 5 coffee drinks, 6 green tea drinks, and 4 black tea drinks) were determined using enzymatic methods., Results: Three zero calorie drinks, 2 sugarless coffee drinks, and 6 green tea drinks contained no sugar. Three coffee drinks contained only sucrose. The orders of median glucose, fructose, and sucrose contents in the categories of beverages containing sugars were as follows: for glucose, fruit juice > energy drink ≥ soda ≫ probiotic drink > black tea drink > sports drink; for fructose, probiotic drink ≥ energy drink > fruit juice > soda ≫ sports drink > black tea drink; and for sucrose, black tea drink > energy drink ≥ probiotic drink > fruit juice > soda > coffee drink ≫ sports drink. The total fructose as a percentage of the total sugar content in the 38 sugar-containing beverages was between 40% and 60%. The total sugar content analyzed was not always equivalent to the carbohydrate content indicated on the nutrition label., Conclusions: These results indicate that information on the actual sugar content of common Japanese beverages is necessary for the exact assessment of beverage-derived sugar intake., Competing Interests: The authors declare that there they have no conflicts of interest.
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- 2023
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7. Maternal High-Fructose Corn Syrup Intake Impairs Corticosterone Clearance by Reducing Renal 11β-Hsd2 Activity via miR-27a-Mediated Mechanism in Rat Offspring.
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Nouchi Y, Munetsuna E, Yamada H, Yamazaki M, Ando Y, Mizuno G, Ikeya M, Kageyama I, Wakasugi T, Teshigawara A, Hattori Y, Tsuboi Y, Ishikawa H, Suzuki K, and Ohashi K
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- Humans, Rats, Animals, Female, Male, Corticosterone, 11-beta-Hydroxysteroid Dehydrogenase Type 2 genetics, Rats, Sprague-Dawley, Zea mays, Kidney, Fructose adverse effects, High Fructose Corn Syrup adverse effects, MicroRNAs genetics
- Abstract
We previously reported that maternal fructose consumption increases blood corticosterone levels in rat offspring. However, the underlying mechanism of action remains unclear. In the present study, we aimed to elucidate the molecular mechanism by which maternal high-fructose corn syrup (HFCS) intake increases circulating GC levels in rat offspring (GC; corticosterone in rodents and cortisol in humans). Female Sprague Dawley rats received HFCS solution during gestation and lactation. The male offspring were fed distilled water from weaning to 60 days of age. We investigated the activities of GC-metabolizing enzymes (11β-Hsd1 and 11β-Hsd2) in various tissues (i.e., liver, kidney, adrenal glands, muscle, and white adipose tissue) and epigenetic modification. 11β-Hsd2 activity decreased in the kidney of the HFCS-fed dams. Moreover, the epigenetic analysis suggested that miR-27a reduced Hsd11b2 mRNA expression in the kidney of offspring. Maternal HFCS-induced elevation of circulating GC levels in offspring may be explained by a decrease in 11β-Hsd2 activity via renal miR-27a expression. The present study may allow us to determine one of the mechanisms of GC elevation in rat offspring that is often observed in the developmental origins of the health and disease (DOHaD) phenomenon.
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- 2023
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8. High-fructose corn syrup intake increases hepatic mitochondrial DNA copy number and methylation in adolescent rats.
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Mizuno G, Yamada H, Munetsuna E, Ando Y, Teshigawara A, Ito M, Kageyama I, Nouchi Y, Wakasugi T, Sakakibara T, Yamazaki M, Ishikawa H, Suzuki K, Hashimoto S, and Ohashi K
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- Rats, Animals, Zea mays metabolism, DNA, Mitochondrial genetics, DNA, Mitochondrial metabolism, Methylation, DNA Copy Number Variations, Liver metabolism, Fructose adverse effects, Fructose metabolism, Mitochondria metabolism, High Fructose Corn Syrup adverse effects, Pediatric Obesity metabolism
- Abstract
High-fructose corn syrup (HFCS) is consumed worldwide. However, it has been demonstrated that an increased intake of sweetened beverages, including those sweetened using fructose, is associated with the development of childhood obesity. It is unknown why the negative effects of fructose are stronger in young persons than in elderly individuals. In recent years, mitochondria have been identified as 1 of the targets of the negative effects of fructose; they possess their own genome called mitochondrial DNA (mtDNA), which encodes genes involved in metabolic functions. We hypothesized that HFCS intake affects mtDNA in the livers of rats, and that the intensity of these effects is age-dependent. The experimental period was divided into 3 parts: childhood and adolescence (postnatal day [PD] 21-60), young adulthood (PD61-100), and adulthood (PD101-140). Rats in the different age groups were assigned to receive either water (control group [CONT]) or a 20% HFCS solution (HFCS). The hepatic mtDNA copy number of the HFCS group was higher than that of the CONT group in childhood and adolescence. In addition, the mtDNA methylation level was increased in the HFCS group in the same experimental period. No significant differences were observed between the CONT and HFCS groups during the other experimental periods. We demonstrated that HFCS has the strongest effect on mtDNA during childhood and adolescence, suggesting a need to analyze the HFCS intake of young people., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2023
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9. Interaction between Prenatal and Postnatal Exposure to High-Fructose Corn Syrup Increases Gene Expression of Tnfa in Hippocampus of Offspring.
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Yamazaki M, Yamada H, Munetsuna E, Ando Y, Kageyama I, Sadamoto N, Nouchi Y, Teshigawara A, Mizuno G, Ishikawa H, Suzuki K, Hashimoto S, and Ohashi K
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- Animals, Female, Male, Pregnancy, Rats, Fructose adverse effects, Gene Expression, Hippocampus, Rats, Sprague-Dawley, Water, High Fructose Corn Syrup adverse effects, Zea mays
- Abstract
Concerns about the negative intergenerational effects of excessive fructose intake are being raised, with evidence suggesting that prenatal fructose intake increases susceptibility to metabolic and cognitive dysfunction later in life. In the present study, we hypothesized that prenatal and postnatal fructose intake acts synergistically to impact on hippocampus of adult offspring. Female Sprague-Dawley rats received distilled water or 20% high-fructose corn syrup (HFCS) solution in addition to standard chow throughout gestation and lactation. Male offspring were weaned at postnatal day 21 (PD21) and were randomized to receive distilled water or 20% HFCS solution until PD60. The following experimental groups were: CC: distilled water dams and post-weaning distilled water, CH: distilled water dams and post-weaning HFCS solution, HC: HFCS solution dams and post-weaning distilled water and HH: HFCS solution dams and post-weaning HFCS solution. The synergistic effect of maternal and post-weaning HFCS intake on the hippocampus was investigated by studying the expression of pro-inflammatory cytokine genes (Tnfa, Il1b, and Il6). At weaning, expression levels of pro-inflammatory cytokines between the offspring of the distilled water and HFCS solution fed dams were not significantly different. At PD60, Tnfa expression was significantly higher in the HH group than in the CC, HC and CH groups, whereas no significant differences were found between the CC, HC, and CH groups. These results suggest that postnatal fructose intake negatively impacts the hippocampus by acting synergistically with prenatal fructose intake.
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- 2023
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10. Effects of High-Fructose Corn Syrup Intake on Glucocorticoid Metabolism in Rats During Childhood, Adolescence and Adulthood.
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Nouchi Y, Munetsuna E, Yamada H, Yamazaki M, Ando Y, Mizuno G, Fujii R, Kageyama I, Wakasugi T, Sakakibara T, Teshigawara A, Ishikawa H, Shimono Y, Suzuki K, Hashimoto S, and Ohashi K
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- Rats, Animals, Glucocorticoids, Zea mays, Lipid Metabolism, Fructose adverse effects, High Fructose Corn Syrup adverse effects
- Abstract
The consumption of high-fructose corn syrup (HFCS) has been increasing in recent decades, especially among children. Some reports suggest that children and adolescents are more sensitive to the adverse effects of fructose intake than adults. However, the underlying mechanism of the difference in vulnerability between adolescence and adulthood have not yet been elucidated. In this study, we attempted to elucidate the different effects of HFCS intake at different growth stages in rats: childhood and adolescence (postnatal day (PD) 21-60), young adulthood (PD60-100), and adulthood (PD100-140). Since alterations in hepatic glucocorticoid (GC) metabolism can cause diseases including insulin resistance, we focused on GC metabolizing enzymes such as 11 beta-hydroxysteroid dehydrogenase 1 and 2 (Hsd11b1 and Hsd11b2) and steroid 5 alpha-reductase 1 (Srd5a1). Western blotting showed an increase in Hsd11b1 expression and a decrease in Hsd11b2 expression in childhood and adolescence but not in adulthood. We also observed changes in Hsd11b1 and Hsd11b2 activities only in childhood and adolescence, consistent with the results of mRNA and protein expression analysis. The effect of high-fructose intake with regards to GC metabolism may therefore vary with developmental stage. This study provides insight into the adverse effects of fructose on GC metabolism in children in the context of increasing rates of HFCS consumption., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)
- Published
- 2022
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11. High-fructose corn syrup intake has stronger effects on the transcription level of hepatic lipid metabolism-related genes, via DNA methylation modification, in childhood and adolescence than in other generations.
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Mizuno G, Yamada H, Munetsuna E, Ando Y, Teshigawara A, Ito M, Kageyama I, Nouchi Y, Wakasugi T, Sakakibara T, Yamazaki M, Fujii R, Ishikawa H, Suzuki K, Hashimoto S, and Ohashi K
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- Animals, Epigenesis, Genetic, Fructose pharmacology, Lipid Metabolism genetics, PPAR alpha genetics, PPAR alpha metabolism, Rats, Zea mays metabolism, Age Factors, DNA Methylation, High Fructose Corn Syrup adverse effects, Liver metabolism
- Abstract
Aims: This study aimed to analyze differences in sensitivity to hepatic lipid metabolism at different ages, through DNA methylation, using an experimental rat model of high-fructose corn syrup (HFCS) intake., Main Methods: The experimental was divided into three periods: childhood and adolescence (postnatal day (PD) 21-60), young adulthood (PD61-100), and adulthood (PD101-140). Rats in the different age groups were assigned to receive either water (C: control group) or 20% HFCS solution (H: HFCS-fed group). We measured hepatic mRNA levels of peroxisome proliferator-activated receptor alpha (Ppara), carnitine palmitoyltransferase 1A (Cpt1a), fatty acid synthase (Fasn), and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (Pgc1a) using real-time PCR. Additionally, we examined the DNA methylation levels of Ppara, Cpt1a, Fasn, and Pgc1a using pyrosequencing., Key Findings: Gene expressions of Cpt1a and Ppara in childhood and adolescence were significantly lower in the H group than in the C group. Conversely, Fasn and Pgc1a expressions were significantly higher in the H group than in the C group. Additionally, there was hypermethylation of Cpt1a and Ppara and hypomethylation of Fasn and Pgc1a in the H groups of childhood and adolescence. However, only one gene expression and methylation change was observed in young adulthood and adulthood groups. We found that HFCS intake in rats had stronger lipid metabolic effects in childhood and adolescence than in other generations, and that its mechanism involved epigenetic regulation., Significance: We anticipate that these research findings will be a breakthrough for elucidating the varying effects of growth stage in the future., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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12. Differential effects of excess high-fructose corn syrup on the DNA methylation of hippocampal neurotrophic factor in childhood and adolescence.
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Kageyama I, Yamada H, Munetsuna E, Yamazaki M, Ando Y, Mizuno G, Fujii R, Nouchi Y, Wakasugi T, Sakakibara T, Teshigawara A, Ishikawa H, Shimono Y, Suzuki K, Hashimoto S, and Ohashi K
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- Adult, Animals, Brain-Derived Neurotrophic Factor genetics, Brain-Derived Neurotrophic Factor metabolism, DNA Methylation, Fructose adverse effects, Fructose metabolism, Hippocampus metabolism, Humans, Male, RNA, Messenger metabolism, Rats, Rats, Sprague-Dawley, Young Adult, Zea mays metabolism, High Fructose Corn Syrup adverse effects
- Abstract
Consumption of fructose-containing beverages such as high-fructose corn syrup (HFCS) is increasing, raising concerns about the negative effects of excessive fructose intake. A recent report indicated that excess HFCS intake impairs hippocampal function. In this study, we focused on neurotrophic factors (NFs) in the hippocampus from the viewpoint of epigenetics to clarify the adverse effects of fructose. We analyzed the effects of HFCS intake on hippocampal function in three age categories: childhood and adolescence (postnatal day (PD) 21-60), young adulthood (PD60-100), and late adulthood (PD100-140). For the experiments, male Sprague-Dawley rats were divided into three age categories, the control group was received distilled water and the HFCS group was received 20% HFCS solution for 40 days in each period. We analyzed mRNA and protein levels for qPCR and western blotting, respectively, of a hippocampal NF, brain-derived neurotrophic factor (Bdnf). HFCS consumption reduced hippocampal Bdnf mRNA and protein expressions in childhood and adolescence. Moreover, pyrosequencing assays revealed increased DNA methylation at the Bdnf promoter in childhood and adolescence. This Bdnf levels reduction may be due to hypermethylation of the promoter regions. It should be noted that this phenomenon was observed only in childhood and adolescence fructose consumption. Our results indicate that the sensitivity of the hippocampus to fructose may vary with age. This study provides insight into the adverse effects of excessive HFCS consumption on the hippocampus in children., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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13. Maternal high-fructose corn syrup consumption causes insulin resistance and hyperlipidemia in offspring via DNA methylation of the Pparα promoter region.
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Ando Y, Yamada H, Munetsuna E, Yamazaki M, Kageyama I, Teshigawara A, Nouchi Y, Fujii R, Mizuno G, Sadamoto N, Ishikawa H, Suzuki K, Hashimoto S, and Ohashi K
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- Animals, DNA Methylation, Female, Fructose adverse effects, PPAR alpha genetics, Pregnancy, Promoter Regions, Genetic, Rats, Rats, Sprague-Dawley, Zea mays, High Fructose Corn Syrup adverse effects, Hyperlipidemias genetics, Insulin Resistance genetics, Metabolic Diseases genetics
- Abstract
There are concerns about the negative effects of fructose intake during pregnancy on the next generation. We have previously reported that offspring from dams fed with fructose during gestation and lactation demonstrate abnormal lipid metabolism in the liver. In this study, we aimed to elucidate the molecular mechanism of the effects of maternal high-fructose corn syrup (HFCS) consumption on offspring. Pregnant Sprague-Dawley rats were fed with 20% HFCS water solution during gestation and lactation. Offspring were put on a normal diet after weaning, and the serum parameters and gene expression patterns were studied at predetermined intervals. Offsprings from pregnant rats fed with 20% HFCS (HFCS group) developed insulin resistance and hyperlipidemia at 60 d of age. RNA-seq analysis demonstrated that peroxisome proliferator-activated receptor α (PPARα) expression is downregulated by maternal HFCS intake. Hepatic Pparα expression in the HFCS group appeared to be suppressed by the enhanced DNA methylation of its promoter region. It is suggested that the development of insulin resistance and hyperlipidemia in the HFCS group may be attributable to aberrant Pparα methylation in the offspring liver. Pparα hypermethylation may be one of molecular mechanism underlying the toxicity of maternal fructose intake., (Copyright © 2022. Published by Elsevier Inc.)
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- 2022
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14. Maternal fructose intake predisposes rat offspring to metabolic disorders via abnormal hepatic programming.
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Munetsuna E, Yamada H, Yamazaki M, Ando Y, Mizuno G, Hattori Y, Kageyama I, Teshigawara A, Nouchi Y, Ishikawa H, Fujii R, Ohta Y, Suzuki K, Shimono Y, Ohashi K, and Hashimoto S
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- Animals, Animals, Newborn, Female, Fructose administration & dosage, Insulin-Like Growth Factor I genetics, Insulin-Like Growth Factor I metabolism, Liver drug effects, Liver metabolism, Longitudinal Studies, Metabolic Diseases chemically induced, Metabolic Diseases metabolism, MicroRNAs genetics, Pregnancy, Prenatal Exposure Delayed Effects chemically induced, Prenatal Exposure Delayed Effects metabolism, Rats, Rats, Sprague-Dawley, Transcriptome, Fructose toxicity, Gene Expression Regulation, Insulin Resistance, Liver pathology, Maternal Nutritional Physiological Phenomena, Metabolic Diseases pathology, Prenatal Exposure Delayed Effects pathology
- Abstract
Given that fructose consumption has increased by more than 10-fold in recent decades, it is possible that excess maternal fructose consumption causes harmful effects in the next generation. This study attempted to elucidate the mechanism of the harmful effects of excessive maternal fructose intake from the perspective of offspring liver function. Female rats during gestation and lactation were fed water containing fructose, and their offspring were fed normal water. We attempted to elucidate the mechanism of fructose-induced transgenerational toxicity by conducting a longitudinal study focusing on hepatic programming prior to disease onset. Impaired Insulin resistance and decreased high-density lipoprotein-cholesterol levels were observed at 160 days of age. However, metabolic disorders were not observed in 60-day-old offspring. Microarray analysis of 60-day-old offspring livers showed the reduction of hepatic insulin-like growth factor-1 (Igf1) mRNA expression. This reduction continued until the rats were aged 160 days and attenuated Igf1 signaling. Hepatic microRNA-29 (miR-29a) and miR-130a, which target Igf1 mRNA, were also found to be upregulated. Interestingly, these miRNAs were upregulated in the absence of metabolic disorder. In this study, we found that maternal fructose intake resulted in dysregulated expression of Igf1 and its target miRNAs in the offspring liver, and that these offspring were more likely to develop metabolic disorders. Abnormal hepatic programming induced by an imbalanced maternal nutritional environment is maintained throughout life, implying that it may contribute to metabolic disorders., (© 2021 Federation of American Societies for Experimental Biology.)
- Published
- 2021
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15. Maternal fructose consumption downregulates hippocampal catalase expression via DNA methylation in rat offspring.
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Mizuno G, Munetsuna E, Yamada H, Yamazaki M, Ando Y, Hattori Y, Kageyama I, Teshigawara A, Nouchi Y, Fujii R, Ishikawa H, Suzuki K, Hashimoto S, Ohashi K, and Shimono Y
- Subjects
- Animals, Brain metabolism, Dietary Sugars adverse effects, Down-Regulation, Feeding Behavior, Female, Hippocampus drug effects, Hippocampus metabolism, Lactation, Male, Mothers, Oxidative Stress, Pregnancy, Prenatal Exposure Delayed Effects, Promoter Regions, Genetic, RNA, Messenger metabolism, Rats, Sprague-Dawley, Weaning, Rats, Antioxidants metabolism, Brain drug effects, Catalase metabolism, DNA Methylation, Epigenesis, Genetic, Fructose adverse effects, Maternal Nutritional Physiological Phenomena
- Abstract
Some studies have demonstrated that excessive fructose consumption negatively impact brain function. Recently, the Developmental Origins of Health and Disease hypothesis - which suggests that maternal nutritional status during gestation and lactation can alter offspring phenotype - has received much attention. In a previous study, we demonstrated that maternal fructose consumption increases levels of lipid peroxides in hippocampi of offspring. The hypothesis in the present study was that maternal fructose intake would affect hippocampal antioxidant enzyme via epigenetic regulation. Upon confirmation of gestation, female rats were assigned to receive either water (control group) or a 20% fructose solution (fructose-fed group). Water or fructose solution were administered to dams from day 1 of gestation to postnatal day 21. Immediately after weaning, hippocampi of offspring were removed for analysis of antioxidant enzyme (Sod1, Sod2, Gpx1, Gpx4, and Cat) messenger RNA transcript levels. Levels of the Cat transcript were significantly lower in the fructose-fed relative to the control group. The Cat protein level was also significantly lower in the fructose-fed relative to the control group as with the messenger RNA transcript levels. Moreover, Cat promoter DNA methylation levels were higher in the fructose-fed group. The present study indicates that maternal fructose consumption may decrease offspring hippocampal Cat transcript levels via altered DNA methylation, which may result in higher levels of oxidative stress due to a decreased ability to neutralize lipid peroxides., (Copyright © 2021 Elsevier Inc. All rights reserved.)
- Published
- 2021
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16. Maternal fructose consumption down-regulates Lxra expression via miR-206-mediated regulation.
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Yamazaki M, Munetsuna E, Yamada H, Ando Y, Mizuno G, Fujii R, Nouchi Y, Kageyama I, Teshigawara A, Ishikawa H, Suzuki K, Shimono Y, Hashimoto S, and Ohashi K
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- Animals, Cholesterol, HDL blood, DNA Methylation, Down-Regulation, Epigenesis, Genetic, Female, Fructose administration & dosage, Gene Expression, Humans, Lactation, Lipid Metabolism, Liver metabolism, Liver X Receptors metabolism, Male, Metabolic Diseases epidemiology, MicroRNAs metabolism, Pregnancy, Prenatal Exposure Delayed Effects metabolism, Rats, Rats, Sprague-Dawley, Fructose adverse effects, Liver X Receptors genetics, Maternal Nutritional Physiological Phenomena, MicroRNAs genetics, Prenatal Exposure Delayed Effects genetics
- Abstract
Maternal fructose consumption affects the metabolic functions of offspring later in life. However, the molecular mechanism remains poorly understood. Differences of microRNA expression profile and DNA methylation status are a candidate mechanism to explain the developmental programming that contributes to the development of a metabolic disorder. This study examined the transgenerational effect of maternal fructose consumption from the perspective of epigenetic modification. To do this, we collected serum and liver tissues from male offspring rats that were exposed to maternal distilled water or 20% fructose water during gestation and lactation. A decreased serum high-density lipoprotein cholesterol (HDL-C) level was observed in the offspring of fructose-fed dams at postnatal day (PD) 160. Given research indicating a role of liver X receptor alpha (LXRA) in cholesterol metabolism, we analyzed Lxra expression. Real-time polymerase chain reaction analysis demonstrated that offspring that were delivered from fructose-fed dams exhibited decreased Lxra gene expression in their liver tissue. There is a well-established association between Lxra expression and the level of DNA methylation and miR-206 expression. Pyrosequencing assays revealed no differences in the level of DNA methylation in the Lxra promoter region, whereas miR-206 expression was increased in the liver at PD 60 and 160. Our data indicate that early-life exposure to maternal fructose results in changing of miR-206 expression level in the liver that suppresses the expression of Lxra. This phenomenon may be associated with the decreased serum HDL-C level in offspring., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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17. Lead selenide-Titanium dioxide heteronanojunction formation by photocatalytic current doubling-induced two-step photodeposition technique.
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Tanaka K, Jin-nouchi Y, Fujishima M, and Tada H
- Abstract
PbSe quantum dots (QDs) were formed on TiO2 by a two-step photodeposition technique. At the first step, UV-light irradiation of TiO2 in an ethanol solution of H2SeO3 yields Se QDs on the TiO2 surface in a highly dispersed state (Se/TiO2). At the second step, UV-light irradiation of Se/TiO2 in an ethanol solution of Pb(ClO4)2 transforms Se QDs into several tens of nanometer-sized cubic deposits identified as PbSe (PbSe/TiO2) by X-ray diffraction, electronic absorption measurements and X-ray photoelectron spectroscopy. Photochronopotentiometry measurements suggested that the PbSe QDs are formed on TiO2 via the Pb(2+) ion-assisted reduction of Se particles., (Copyright © 2015. Published by Elsevier Inc.)
- Published
- 2015
- Full Text
- View/download PDF
18. PbS quantum dot-sensitized photoelectrochemical cell for hydrogen production from water under illumination of simulated sunlight.
- Author
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Jin-nouchi Y, Hattori T, Sumida Y, Fujishima M, and Tada H
- Published
- 2010
- Full Text
- View/download PDF
19. Ultrafast photodeposition of size-controlled PbS quantum dots on TiO2.
- Author
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Jin-nouchi Y, Akita T, and Tada H
- Published
- 2010
- Full Text
- View/download PDF
20. [Assessment of exercise-induced silent myocardial ischemia by dipyridamole thallium imaging. (2). Its significance in Q wave myocardial infarction].
- Author
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Jin-nouchi Y, Furuno T, Yamasaki F, Yabe T, Kitaoka H, Chikamori T, Kawai K, and Doi Y
- Subjects
- Aged, Coronary Angiography, Electrocardiography, Female, Humans, Male, Middle Aged, Myocardial Infarction physiopathology, Radionuclide Imaging, Thallium Radioisotopes, Dipyridamole, Exercise Test, Myocardial Infarction diagnostic imaging, Vasodilator Agents
- Abstract
The clinical significance of silent myocardial ischemia (SMI) in the elderly was assessed in 91 patients with Q wave infarction who showed ischemic ST depression during treadmill stress testing, as well as reversible defect (RD) during dipyridamole thallium imaging. They were divided into two groups (47 patients with silent ST depression and 44 patients with painful ST depression) and compared for scintigraphic and coronary arteriographic features, and prognosis. There was no significant difference in age, gender and site of infarction between the two groups. The prevalence of single and double vessel coronary stenosis was higher in patients with SMI (66%) than in those with painful ischemia (p < 0.05). The results of treadmill stress testing showed a longer exercise duration (4.7 +/- 1.7 vs. 4.1 +/- 1.8 min) and higher maximal heart rate (138 +/- 15/vs. 126 +/- 20/min) in patients with SMI than in those with painful ischemia (p < 0.01). Dipyridamole thallium imaging revealed a larger infact (18.8 +/- 9.1 vs. 14.6 +/- 10.2 segments) in patients with SMI than in those with painful ischemia (p < 0.05). The prevalence of RD in the area of infarction was also higher in patients with SMI (74%) than in those with painful ischemia (45%) (p < 0.05). Although a higher proportion of the patients with painful ischemia (42%) underwent CABG or PTCA as their initial therapy, compared with those with SMI (25%) (ns), there was no difference in the cardiac event rate between the two groups who were initially treated medically. Dipyridamole thallium imaging is useful in the assessment of SMI in elderly patients with Q wave myocardial infarction. Those with SMI may have a larger infarct and a higher prevalence of ischemia localized within the infarction than those with painful ischemia.
- Published
- 1998
- Full Text
- View/download PDF
21. [Assessment of exercise-induced silent myocardial ischemia by dipyridamole thallium imaging: (1). Its significance in stable angina pectoris].
- Author
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Jin-nouchi Y, Yabe T, Furuno T, Yamasaki F, Matsumura Y, Chikamori T, Kawai K, and Doi Y
- Subjects
- Aged, Angina Pectoris diagnosis, Angina Pectoris physiopathology, Coronary Angiography, Electrocardiography, Female, Humans, Male, Middle Aged, Radionuclide Imaging, Angina Pectoris diagnostic imaging, Dipyridamole, Exercise Test, Vasodilator Agents
- Abstract
To assess the clinical significance of silent myocardial ischemia (SMI) in the elderly, 113 patients with stable angina who showed ischemic ST depression during treadmill stress testing were studied by dipyrimadole thallium imaging and coronary arteriography. They were divided into two groups: 44 patients with silent ST depressions and 69 patients with painful ST depressions. The groups were compared for scintigraphic and coronary arteriographic features as well as prognosis. There was a significantly greater proportion of older patients (> or = 65 years) in the group with SMI (64%) than in the group with painful ischemia (38%) (p < 0.01), although there was no difference in the mean ages of the two groups. The prevalence of multivessel coronary stenosis was not significantly different between the two groups (45% in the SMI group and 61% in the group with painful ischemia). Treadmill stress testing showed no differences in exercise duration, maximal heart rate, maximal systolic blood pressure, or maximal ST depression between the two groups. Dipyrimadamole thallium imaging revealed similar results in the site of reversible defects (RD), i.e. 76% in the anterior area and 24% in the inferior area in patients with SMI, and 83% in the anterior area and 17% in the inferior area in patients with painful ischemia. However, the size of RD was significantly smaller in patients with SMI, i.e. 14.6 +/- 6.1 segments in patients with SMI and 18.7 +/- 8.3 segments in patients with painful ischemia (p < 0.05). Although a significantly higher proportion of patients with painful ischemia (48%) underwent PTCA or CABG as their initial therapy as compared to those with SMI (16%), there was no significant difference in the cardiac event rate between the two groups initially treated medically. Among patients with stable angina, those with SMI may have a smaller amount of ischemic myocardium and may be older in a greater proportion than those with painful ischemia. Dipyrimadole thallium imaging is useful in the assessment of SMI in the elderly.
- Published
- 1998
- Full Text
- View/download PDF
22. [Hemodynamic difference accounted for the orientation of a Björk-Shiley mitral prosthesis: a color Doppler echocardiographic study].
- Author
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Jin-Nouchi Y, Doi Y, Odawara H, Yonezawa Y, Ozawa T, Yokoi T, Yamamoto K, Nishimura N, Ohwaki T, and Nagamori S
- Subjects
- Aged, Female, Hemodynamics, Humans, Male, Middle Aged, Mitral Valve diagnostic imaging, Mitral Valve surgery, Mitral Valve Insufficiency etiology, Regional Blood Flow, Echocardiography, Doppler, Heart Valve Prosthesis adverse effects, Mitral Valve physiopathology
- Abstract
To determine whether the orientation of the major orifice of a mitral tilting disc prosthesis affects hemodynamics, intracavitary blood flow patterns were studied in 45 patients with well-functioning Björk-Shiley mitral prosthesis using color Doppler flow imaging. The major orifice was oriented towards the septum in 23 patients (12 men, 11 women, age 58 +/- 11 years; group S), and towards the posterior wall in 22 patients (8 men, 14 women, age 55 +/- 9 years; group P). 1) The left ventricular end-diastolic dimensions (S: 4.8 +/- 0.9 cm, P: 5.2 +/- 1.0 cm), end-systolic dimensions (S: 3.6 +/- 0.9 cm, P: 3.8 +/- 1.2 cm), and left atrial dimensions (S: 5.0 +/- 1.0 cm, P: 4.7 +/- 0.9 cm) did not differ significantly between the 2 groups. 2) The peak mitral flow velocities (S: 1.43 +/- 0.38 m/sec, P: 1.43 +/- 0.27 m/sec), pressure gradients (S: 8.5 +/- 4.0 mmHg, P: 8.4 +/- 3.1 mmHg), and pressure half-times (S: 94.0 +/- 19.0 msec, P: 86.5 +/- 21.7 msec) did not differ significantly between the 2 groups. 3) Although mitral regurgitation was detected in 8 patients (35%) in the S group and in 2 patients (9%) in the P group, hemodynamically significant regurgitation was detected in only 4 patients in the S group (3 mild, one moderate). 4) The patients in the S group had reversed intracavitary blood flow; mitral flow was first directed towards the left ventricular outflow tract during diastole, while the outflow pattern was displaced into the left ventricular inflow tract.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1992
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