Naoki Fujita

Mie University, Tu, Mie, Japan

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Publications (75)313.09 Total impact

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    ABSTRACT: Diabetes mellitus (DM), non-alcoholic fatty liver (NAFL), and obesity are associated with elevated branched-chain amino acid (BCAA) levels, but the mechanism and significance of this has not been elucidated. Eighty-four subjects were enrolled including 43 with DM. Serum BCAA levels were positively correlated with waist-hip ratio and ALT. Serum BCAA levels in subjects with DM were higher than non-DM and those in subjects with NAFL were also higher than non-NAFL. Treatment with pioglitazone and alogliptin (19 of 43 DM subjects) improved serum haemoglobin A1c and decreased BCAA levels. The decrease in BCAAs with improved glucose metabolism suggests that abnormal glucose metabolism is also a factor in elevated BCAA levels. Copyright © 2015 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
    Obesity Research & Clinical Practice 01/2015; DOI:10.1016/j.orcp.2015.01.003 · 0.70 Impact Factor
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    Hepatology Research 10/2014; 44(10). DOI:10.1111/hepr.12217 · 2.07 Impact Factor
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    ABSTRACT: Very few reports thus far have clinically elucidated the advantages of a nutrition support team (NST) in the field of liver diseases. The present study retrospectively analyzed whether nutrition therapy for liver cirrhosis (LC), performed by a multidisciplinary team that includes registered dieticians, improves survival rates. In study 1, we compared survival rates between two groups of patients with LC to elucidate the effects of nutrition management by registered dieticians. The first group was comprised of 101 patients that received no dietary counseling from a dietician, and the second group was comprised of 133 patients that received nutritional counseling following nutrition assessment. In study 2, we split the patients who received nutritional counseling in study 1 into two groups and compared their survival rates with the objective of investigating the effects of a multidisciplinary team approach on survival rate. The first group was comprised of 51 patients that, in addition to regular nutritional counseling given by a dietician, regularly attended courses on liver disease given every 3 to 6 mo. The second group was comprised of 82 patients that did not attend the liver-disease courses. During study 1, 34 patients in the first group and 20 patients in the second group died, representing a significant difference (P < 0.05). This difference was even more pronounced in the subset of patients classified as Child-Pugh class A (P < 0.01), but no differences were seen among patients in classes B and C (P = 0.378). During study 2, four patients in the first group and 15 patients in the second group died, representing a significant difference (P < 0.05). This study showed that nutritional intervention using a multidisciplinary team during the treatment of LC improves survival rates and quality of life of the patients.
    Nutrition 11/2013; 29(11-12):1418-1421. DOI:10.1016/j.nut.2013.05.016 · 3.05 Impact Factor
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    ABSTRACT: Background/Aims: Iron overload and hyperglycemia are common findings in patients with chronic hepatitis C (CHC). The aim of this study was to determine the relation of serum ferritin and hepatic hepcidin expression with glucose metabolic parameters and to evaluate whether long term phlebotomy lowers the risk of new-onset diabetes in CHC patients. Methodology: Hepatic hepcidin mRNA expression was measured in 28 CHC patients and their relation with clinical parameters and histological findings was evaluated. Ninety-two patients without type 2 diabetes were divided into two groups: a phlebotomy group underwent an initial period of phlebotomy and maintenance phlebotomy was performed; data obtained in CHC patients that declined to receive phlebotomy were used as control. Results: Hepatic hepcidin expression was positively correlated with body mass index and glucose metabolic parameters. A total number of five patients had onset of type 2 diabetes over 38.9 months of follow-up. Long-term phlebotomy tended to lower the risk of new-onset diabetes compared with control CHC patients. In addition, high ferritin levels predicted further episodes of diabetes in control patients. Conclusions: Iron overload is a risk for the development of diabetes in patients with CHC and that reduction of body iron stores lowers this risk.
    Hepato-gastroenterology 10/2013; 60(127):1736-41. DOI:10.5754/hge12472 · 0.91 Impact Factor
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    Journal of Gastroenterology and Hepatology 08/2013; 28(8):1256. DOI:10.1111/jgh.12323 · 3.33 Impact Factor
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    ABSTRACT: Long-term supplementation with branched-chain amino acids (BCAA) is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05). The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.
    PLoS ONE 07/2013; 8(7):e70309. DOI:10.1371/journal.pone.0070309 · 3.53 Impact Factor
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  • Journal of Hepatology 04/2013; 58:S216-S217. DOI:10.1016/S0168-8278(13)60530-9 · 10.40 Impact Factor
  • Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 02/2013; 48(1):32-8.
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    Journal of Gastroenterology and Hepatology 06/2012; 27(6):1129. DOI:10.1111/j.1440-1746.2012.07139.x · 3.33 Impact Factor
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    ABSTRACT: Chronic hepatic encephalopathy is a characteristically reversible neuropsychiatric disorder that occurs mainly in patients with liver cirrhosis. The brain regions critically involved in the pathophysiology of cirrhosis are not clear. Magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) is a valuable tool for evaluating structural brain changes in many neurodegenerative diseases. We performed an MRI scan on 18 patients with liver cirrhosis and 16 age-matched healthy controls. We evaluated brain regional structural changes, regional differences and the relationship of these changes with the blood levels of ammonia and the results of neuropsychological tests in patients with cirrhosis. The VBM showed reduction in the volume of gray matter in the cerebellum and occipital lobe and in the volume of white matter in the cingulate, parietal, temporal, occipital lobe and precentral area in cirrhotic patients compared with controls. There were significant correlations between the volume of these regions with the plasma levels of ammonia and the results of neuropsychological tests. Voxel-based analysis of MRI revealed evidence for structural abnormalities of brain in patients with cirrhosis. Abnormal function in the above regions may account for the ammonia-mediated changes and neuropsychological deficits in hepatic encephalopathy.
    Metabolic Brain Disease 05/2012; 27(4). DOI:10.1007/s11011-012-9314-x · 2.40 Impact Factor
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    ABSTRACT: Ninety seven patients with chronic hepatitis C (CHC) and 72 with non-alcoholic fatty liver disease (NAFLD) were enrolled. Increased visceral fat area (VFA) was associated with high values of HbA1c. The variables associated with a high risk of new-onset diabetes had a VFA>101 cm(2) in CHC, but not in NAFLD.
    Diabetes research and clinical practice 12/2011; 94(3):468-70. DOI:10.1016/j.diabres.2011.09.016 · 2.74 Impact Factor
  • Naoki Fujita, Yoshiyuki Takei
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    ABSTRACT: Drinking excessive amounts of alcohol regularly for years is toxic to almost every tissue of the body. On the other hand, epidemiological and clinical evidence shows that light-to-moderate drinking is associated with a reduced risk of coronary heart disease, total and ischemic stroke, and mortality. In the past two decades, metabolic syndrome, the combination of obesity, hypertension, dyslipidemia and hyperglycemia, are all also recognized as major cardiovascular risk factors, has given rise to much clinical and research attention, because of its high prevalence in the world. Therefore, it is of interest to evaluate the overall associations of alcohol consumption with the development of metabolic syndrome. Recently, the protective, detrimental or J-shaped associations have been reported between alcohol consumption and metabolic syndrome. This controversy may be due to the complex mechanistic relation between alcohol consumption and each component of metabolic syndrome, and almost all studies have various limitations and problem points. Prospective studies are therefore needed to confirm the association between alcohol consumption and prevalence of metabolic syndrome, and to assess the influence of alcohol drinking patterns and other possible factors, such as smoking, physical activity, socioeconomic status, education, occupation, diet and exercise. This article reviews the relation of alcohol consumption and components of metabolic syndrome, and discusses the epidemiological evidence for alcohol's putative vascular protective effects and plausible underlying biological mechanisms.
    Hepatology Research 04/2011; 41(4):287-95. DOI:10.1111/j.1872-034X.2011.00787.x · 2.22 Impact Factor
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    ABSTRACT: Aim:  Hepcidin is a key regulator of systemic iron metabolism and its expression is modulated by hepatitis C virus (HCV) infection. Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 act as negative regulators of the Jak/signal transducers and activators of transcription signaling pathway. In this study, we investigated how HCV infection modulates SOCS-1 and SOCS-3 production and how these SOCS proteins affect hepcidin production. Methods:  The effects of SOCS-1 and SOCS-3 on hepcidin production were investigated using a complete genome, HCV replicon system. Results:  Unexpectedly, basal expression levels of hepcidin (HAMP) mRNA and the bioactive form of hepcidin protein, hepcidin-25, were significantly higher in replicon cells. Regardless of HCV infection, STAT3 was activated in response to interleukin-6 (IL-6), but this activation was greater in replicon cells than in cured cells. Basal expression of the SOCS-3 protein was enhanced, but basal expression of SOCS-1 protein was reduced, in replicon cells. Expression of SOCS-3 increased dramatically in response to IL-6 stimulation but expression of SOCS-1 was not induced by IL-6. Interestingly, silencing of SOCS-1 and SOCS-3 gene expression enhanced STAT3 activation and HAMP gene expression. In addition, overexpression of SOCS-1 protein strongly suppressed STAT3 activation and HAMP gene expression. Conclusions:  This in vitro study shows that SOCS-3 expression was enhanced but SOCS-1 expression was reduced by HCV infection. The upregulation of hepcidin induced by IL-6 was found to be negatively regulated by SOCS-1 and SOCS-3. The modulation of SOCS1 and SOCS3 in HCV-infected hepatocytes may explain, at least in part, the relative shortage of hepcidin production in CH-C.
    Hepatology Research 02/2011; 41(4):364-74. DOI:10.1111/j.1872-034X.2011.00777.x · 2.22 Impact Factor
  • Clinical Nutrition Supplements 01/2011; 6(1):136-136. DOI:10.1016/S1744-1161(11)70349-0
  • Naoki Fujita, Yoshiyuki Takei
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    ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is a major causative agent of chronic liver disease worldwide, but the actual mechanisms responsible for liver injury remain unclear. NAFLD includes a spectrum of clinical entities ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with possible evolution to cirrhosis and hepatocellular carcinoma. Iron is considered a putative element that interacts with oxygen radicals in inducing liver damage/fibrosis and insulin resistance. The role of hepatic iron in the progression of NASH remains controversial, but in some patients, iron may have a role in the pathogenesis of NASH. Though genetic factors, insulin resistance, dysregulation of iron-regulatory molecules, erythrophagocytosis by Kupffer cells may be responsible for hepatic iron accumulation in NASH, exact mechanisms involved in iron overload remain to be clarified. Iron reduction therapy such as phlebotomy or iron-restricted diet may be promising in patients with NAFLD/NASH to reduce hepatic injury as well as insulin resistance. Larger controlled trials of longer duration are warranted to assess the long-term clinical benefit of phlebotomy and/or iron-restricted diet in NAFLD/NASH.
    Advances in clinical chemistry 01/2011; 55:105-32. DOI:10.1016/B978-0-12-387042-1.00006-X · 4.30 Impact Factor
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    ABSTRACT: Recent development of proteomic array technology, including protein profiling coupling ProteinChip array with surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF/MS), provides a potentially powerful tool for discovery of new biomarkers by comparison of its profiles according to patient phenotypes. We used this approach to identify the host factors associated with treatment response in patients with chronic hepatitis C (CHC) receiving a 48-wk course of pegylated interferon (PEG-IFN) alpha 2b plus ribavirin (RBV). Protein profiles of pretreatment serum samples from 32 patients with genotype 1b and high viral load were conducted by SELDI-TOF/MS by using the three different ProteinChip arrays (CM10, Q10, IMAC30). Proteins showed significantly different peak intensities between sustained virological responders (SVRs), and non-SVRs were identified by chromatography, SDS-PAGE, TOF/MS and tandem mass spectrometry (MS/MS) assay. Eleven peak intensities were significantly different between SVRs and non-SVRs. The three SVR-increased peaks could be identified as two apolipoprotein (Apo) fragments and albumin and, among the eight non-SVR-increased proteins, four peaks identified as two iron-related and two fibrogenesis-related protein fragments, respectively. Multivariate analysis showed that the serum ferritin and three peak intensity values (Apo A1, hemopexin and transferrin) were independent variables associated with SVRs, and the area under the receiver operating characteristic (ROC) curves for SVR prediction by using the Apo A1/hemopexin and hemopexin/transferrin were 0.964 and 0.936. In conclusion, pretreatment serum protein profiling by SELDI-TOF/MS is variable for identification of response-related host factors, which are useful for treatment efficacy prediction in CHC receiving PEG-IFN plus RBV. Our data also may help us understand the mechanism for treatment resistance and development of more effective antiviral therapy targeted toward the modulation of lipogenesis or iron homeostasis in CHC patients.
    Molecular Medicine 10/2010; 17(1-2):70-8. DOI:10.2119/molmed.2010.00124 · 4.82 Impact Factor
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    ABSTRACT: Aim:  To clarify the impact of visceral fat on chronic liver diseases such as non-alcoholic fatty liver disease (NAFLD) and hepatitis C, we investigated the effects of lifestyle modifications on the amount of visceral fat, liver biochemistry and serum ferritin levels in patients with liver disease. Methods:  Eighty-two patients (NAFLD, n = 37; hepatitis C, n = 45) were advised to adopt lifestyle modifications, including dietary changes and exercise, and these were maintained for 6 months. Bodyweight, percentage of body fat, visceral fat area (VFA) and serum alanine aminotransferase (ALT) and ferritin were measured before and after intervention. Results:  In NAFLD, the mean VFA of 134.5 cm(2) was significantly reduced to 125.3 cm(2) after 6 months (P < 0.001). ALT levels improved significantly between the values measured before and after intervention (P = 0.039). The VFA prior to intervention was 100 cm(2) in hepatitis C patients and it was reduced significantly after 6 months to 95.6 cm(2) (P < 0.001). ALT levels also improved significantly in the hepatitis C patients (P < 0.001). The serum ferritin levels also reduced in these patients. Improvements in serum ALT and ferritin levels correlated with the amount of visceral fat reduction in both groups (P = 0.046, P = 0.008, respectively). Conclusion:  These findings demonstrate that restriction of calorie and iron intake results in reduction of visceral fat, liver enzymes and ferritin in patients with chronic liver disease. Visceral fat may be a central target for future interventions, not only in NAFLD but also in hepatitis C.
    Hepatology Research 09/2010; 40(12):1188-94. DOI:10.1111/j.1872-034X.2010.00724.x · 2.22 Impact Factor
  • Journal of Hepatology 04/2010; 52. DOI:10.1016/S0168-8278(10)60259-0 · 10.40 Impact Factor
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    ABSTRACT: Reactive oxygen species (ROS) and reactive nitrogen species (RNS) can play an important role in cellular injury and carcinogenesis of gastric epithelial cells infected with Helicobacter pylori. 8-OH-deoxy guanosine (8-OHdG) and 8-nitroguanine (8-NG) are markers for ROS- and RNS-mediated DNA oxidation, respectively. In this study, RNS-mediated DNA damage in gastric mucosa was observed directly using a newly developed antibody to 8-NG to clarify how H. pylori infection causes nitrative DNA damage to gastric epithelial cells. Immunohistochemistry with anti-8-OHdG and anti-8-NG antibodies was performed on gastric tissue samples from 45 patients (25 men and 20 women) with H. pylori-positive gastritis and 19 patients (11 men and 8 women) exhibiting successful H. pylori eradication. Histologic factors for gastric mucosal inflammation were graded according to the guidelines of the Updated Sydney system. In corpus mucosa, 8-OHdG and 8-NG production were significantly associated with the degree of glandular atrophy, infiltration of chronic inflammatory cells and intestinal metaplasia in the glandular epithelial cells. Successful H. pylori eradication resulted in a significant reduction of chronic inflammatory cell infiltration and neutrophilic activity. Mean 8-OHdG production was lower after H. pylori eradication in both corpus and antral mucosa (p = .022 and .049, respectively). However, the reduction in 8-NG exhibited was more pronounced than the reduction of 8-OhdG (p = .004 and .007, respectively). Helicobacter pylori infection can induce inflammatory cells infiltration, which evokes DNA damage of gastric epithelial cells through ROS and RNS production. 8-NG might be a more sensitive biomarker than 8-OHdG for H. pylori-induced DNA damage in gastric mucosa.
    Helicobacter 12/2009; 14(6):552-8. DOI:10.1111/j.1523-5378.2009.00719.x · 2.99 Impact Factor

Publication Stats

906 Citations
313.09 Total Impact Points

Institutions

  • 2004–2014
    • Mie University
      • • Department of Gastroenterology and Hepatology
      • • Center for Physical and Mental Health
      Tu, Mie, Japan
    • Mie-chuo Medical Center
      Matsusaka, Mie, Japan
  • 2009
    • Suzuka University of Medical Science
      Kambe, Mie, Japan