Base de dados : MEDLINE
Pesquisa : C18.654.521.500.133.699.160 [Categoria DeCS]
Referências encontradas : 1250 [refinar]
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[PMID]:29229391
[Au] Autor:Park JS; Shim YJ; Kang BH; Lee WK; Min BH
[Ad] Endereço:Department of Pharmacology, College of Medicine, Korea University, Seoul, Republic of Korea.
[Ti] Título:Hepatocyte-specific clusterin overexpression attenuates diet-induced nonalcoholic steatohepatitis.
[So] Source:Biochem Biophys Res Commun;495(2):1775-1781, 2018 01 08.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Clusterin is a multifunctional glycoprotein that plays important roles and is up-regulated in liver diseases such as hepatitis and hepatocellular carcinoma. However, little is known about the significance of clusterin in the pathogenesis of non-alcoholic steatohepatitis (NASH). The aim of this study is to examine the role of clusterin in progression of steatohepatitis in mice fed a methionine and choline deficient (MCD) diet. We generated hepatocyte-specific clusterin overexpression (hCLU-tg) mice, and hCLU-tg mice showed lower levels of hepatic triglycerides, less infiltration of macrophages and reduction of TNF-α, activation of Nrf-2 than wild-type littermates fed the MCD diet. Also, sustained clusterin expression in liver ameliorated hepatic fibrogenesis by reducing the activation of hepatic stellate cells by MCD diet. Sustained expression of clusterin in liver functioned as a preconditioning stimulus and prevented MCD diet-induced severe steatohepatitis injury via Nrf2 activation. These results demonstrate a novel function of clusterin as an immune preconditioning regulator in various inflammatory diseases including steatohepatitis.
[Mh] Termos MeSH primário: Clusterina/metabolismo
Hepatócitos/metabolismo
Hepatopatia Gordurosa não Alcoólica/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Deficiência de Colina/complicações
Deficiência de Colina/metabolismo
Clusterina/genética
Dieta/efeitos adversos
Modelos Animais de Doenças
Fígado/metabolismo
Fígado/patologia
Masculino
Metionina/deficiência
Camundongos
Camundongos Transgênicos
Fator 2 Relacionado a NF-E2/metabolismo
Hepatopatia Gordurosa não Alcoólica/etiologia
Hepatopatia Gordurosa não Alcoólica/metabolismo
Estresse Oxidativo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Clu protein, mouse); 0 (Clusterin); 0 (NF-E2-Related Factor 2); 0 (Nfe2l2 protein, mouse); 0 (RNA, Messenger); AE28F7PNPL (Methionine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE


  2 / 1250 MEDLINE  
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[PMID]:29244873
[Au] Autor:Yoo W; Gjuka D; Stevenson HL; Song X; Shen H; Yoo SY; Wang J; Fallon M; Ioannou GN; Harrison SA; Beretta L
[Ad] Endereço:Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
[Ti] Título:Fatty acids in non-alcoholic steatohepatitis: Focus on pentadecanoic acid.
[So] Source:PLoS One;12(12):e0189965, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and ranges from isolated steatosis to NASH. To determine whether circulating fatty acids could serve as diagnostic markers of NAFLD severity and whether specific fatty acids could contribute to the pathogenesis of NASH, we analyzed two independent NAFLD patient cohorts and used the methionine- and choline-deficient diet (MCD) NASH mouse model. We identified six fatty acids that could serve as non-invasive markers of NASH in patients with NAFLD. Serum levels of 15:0, 17:0 and 16:1n7t negatively correlated with NAFLD activity scores and hepatocyte ballooning scores, while 18:1n7c serum levels strongly correlated with fibrosis stage and liver inflammation. Serum levels of 15:0 and 17:0 also negatively correlated with fasting glucose and AST, while 16:1n7c and 18:1n7c levels positively correlated with AST and ferritin, respectively. Inclusion of demographic and clinical parameters improved the performance of the fatty acid panels in detecting NASH in NAFLD patients. The panel [15:0, 16:1n7t, 18:1n7c, 22:5n3, age, ferritin and APRI] predicted intermediate or advanced fibrosis in NAFLD patients, with 82% sensitivity at 90% specificity [AUROC = 0.92]. 15:0 and 18:1n7c were further selected for functional studies in vivo. Mice treated with 15:0-supplemented MCD diet showed reduced AST levels and hepatic infiltration of ceroid-laden macrophages compared to MCD-treated mice, suggesting that 15:0 deficiency contributes to liver injury in NASH. In contrast, 18:1n7c-supplemented MCD diet didn't affect liver pathology. In conclusion, 15:0 may serve as a promising biomarker or therapeutic target in NASH, opening avenues for the integration of diagnosis and treatment.
[Mh] Termos MeSH primário: Ácidos Graxos/metabolismo
Hepatócitos/metabolismo
Hepatopatia Gordurosa não Alcoólica/metabolismo
[Mh] Termos MeSH secundário: Animais
Colina/metabolismo
Deficiência de Colina/genética
Deficiência de Colina/metabolismo
Modelos Animais de Doenças
Ácidos Graxos/isolamento & purificação
Hepatócitos/patologia
Seres Humanos
Fígado/metabolismo
Fígado/patologia
Metionina/deficiência
Metionina/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Hepatopatia Gordurosa não Alcoólica/dietoterapia
Hepatopatia Gordurosa não Alcoólica/patologia
Triglicerídeos/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids); 0 (Triglycerides); AE28F7PNPL (Methionine); CCW02D961F (pentadecanoic acid); N91BDP6H0X (Choline)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180102
[Lr] Data última revisão:
180102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189965


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[PMID]:27773935
[Au] Autor:Meng Q; Duan XP; Wang CY; Liu ZH; Sun PY; Huo XK; Sun HJ; Peng JY; Liu KX
[Ad] Endereço:Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian 116044, China.
[Ti] Título:Alisol B 23-acetate protects against non-alcoholic steatohepatitis in mice via farnesoid X receptor activation.
[So] Source:Acta Pharmacol Sin;38(1):69-79, 2017 Jan.
[Is] ISSN:1745-7254
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from the traditional Chinese medicine rhizoma alismatis, which exhibits a number of pharmacological activities, including anti-hepatitis virus, anti-cancer and antibacterial effects. In this study we examined whether AB23A protected against non-alcoholic steatohepatitis (NASH) in mice, and the mechanisms underlying the protective effects. NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4 weeks. The mice were simultaneously treated with AB23A (15, 30, and 60 mg·kg ·d , ig) for 4 weeks. On the last day, blood samples and livers were collected. Serum liver functional enzymes, inflammatoru markers were assessed. The livers were histologically examined using H&E, Oil Red O, Masson's trichrome and Sirius Red staining. Mouse primary hepatocytes were used for in vitro experiments. The mechanisms underlying AB23A protection were analyzed using siRNA, qRT-PCR, and Western blot assays. AB23A treatment significantly and dose-dependently decreased the elevated levels of serum ALT and AST in MCD diet-fed mice. Furthermore, AB23A treatment significantly reduced hepatic triglyceride accumulation, inflammatory cell infiltration and hepatic fibrosis in the mice. AB23A-induced decreases in serum and hepatic lipids were related to decreased hepatic lipogenesis through decreasing hepatic levels of SREBP-1c, FAS, ACC1 and SCD1 and increased lipid metabolism via inducing PPARα, CPT1α, ACADS and LPL. The reduction in inflammatory cell infiltration corresponded to deceased serum levels of mKC and MCP-1 and decreased hepatic gene expression of MCP-1 and VCAM-1. The reduction in hepatic fibrosis was correlated with decreased hepatic gene expression of fibrosis markers. The protective effects of AB23A were FXR-dependent, because treatment with the FXR agonist CDCA mimicked AB23A-induced hepato-protection in the mice, whereas co-administration of FXR antagonist guggulsterone abrogated AB23A-induced hepato-protection. In mouse primary hepatocytes, FXR gene silencing abrogated AB23A-induced changes in gene expression of Apo C-II, CPT1α, ACADS and LPL. AB23A produces protective effects against NASH in mice via FXR activation.
[Mh] Termos MeSH primário: Colestenonas/farmacologia
Hepatopatia Gordurosa não Alcoólica/prevenção & controle
Receptores Citoplasmáticos e Nucleares/agonistas
[Mh] Termos MeSH secundário: Animais
Ácido Quenodesoxicólico/farmacologia
Colestenonas/antagonistas & inibidores
Deficiência de Colina
Relação Dose-Resposta a Droga
Fibrose/patologia
Expressão Gênica/efeitos dos fármacos
Hepatócitos/metabolismo
Metabolismo dos Lipídeos/efeitos dos fármacos
Lipogênese/efeitos dos fármacos
Fígado/enzimologia
Fígado/metabolismo
Fígado/patologia
Masculino
Metionina/deficiência
Camundongos
Pregnenodionas/farmacologia
Cultura Primária de Células
Substâncias Protetoras/farmacologia
Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholestenones); 0 (Pregnenediones); 0 (Protective Agents); 0 (Receptors, Cytoplasmic and Nuclear); 0 (alisol B 23-acetate); 0 (farnesoid X-activated receptor); 0GEI24LG0J (Chenodeoxycholic Acid); A4PW148END (pregna-4,17-diene-3,16-dione); AE28F7PNPL (Methionine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180101
[Lr] Data última revisão:
180101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1038/aps.2016.119


  4 / 1250 MEDLINE  
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[PMID]:28895242
[Au] Autor:Ikawa-Yoshida A; Matsuo S; Kato A; Ohmori Y; Higashida A; Kaneko E; Matsumoto M
[Ad] Endereço:Chugai Research Institute for Medical Science, Inc., Gotemba, Japan.
[Ti] Título:Hepatocellular carcinoma in a mouse model fed a choline-deficient, L-amino acid-defined, high-fat diet.
[So] Source:Int J Exp Pathol;98(4):221-233, 2017 Aug.
[Is] ISSN:1365-2613
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Hepatocellular carcinoma (HCC) is a common cancer worldwide and represents the outcome of the natural history of chronic liver disease. The growing rates of HCC may be partially attributable to increased numbers of people with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). However, details of the liver-specific molecular mechanisms responsible for the NAFLD-NASH-HCC progression remain unclear, and mouse models that can be used to explore the exact factors that influence the progression of NAFLD/NASH to the more chronic stages of liver disease and subsequent HCC are not yet fully established. We have previously reported a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) as a dietary NASH model with rapidly progressive liver fibrosis in mice. The current study in C57BL/6J mice fed CDAHFD provided evidence for the chronic persistence of advanced hepatic fibrosis in NASH and disease progression towards HCC in a period of 36 weeks. When mice fed CDAHFD were switched back to a standard diet, hepatic steatosis was normalized and NAFLD activity score improved, but HCC incidence increased and the phenotype of fibrosis-associated HCC development was observed. Moreover, when mice continued to be fed CDAHFD for 60 weeks, HCC further developed without severe body weight loss or carcinogenesis in other organs. The autochthonous tumours showed a variety of histological features and architectural patterns including trabecular, pseudoglandular and solid growth. The CDAHFD mouse model might be a useful tool for studying the development of HCC from NAFLD/NASH, and potentially useful for better understanding pathological changes during hepatocarcinogenesis.
[Mh] Termos MeSH primário: Carcinoma Hepatocelular
Transformação Celular Neoplásica
Deficiência de Colina/metabolismo
Dieta Hiperlipídica
Neoplasias Hepáticas/patologia
Hepatopatia Gordurosa não Alcoólica/patologia
[Mh] Termos MeSH secundário: Animais
Colina/metabolismo
Colina/farmacologia
Modelos Animais de Doenças
Masculino
Camundongos Endogâmicos C57BL
Hepatopatia Gordurosa não Alcoólica/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
N91BDP6H0X (Choline)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170913
[St] Status:MEDLINE
[do] DOI:10.1111/iep.12240


  5 / 1250 MEDLINE  
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[PMID]:28711489
[Au] Autor:Mitsumoto K; Watanabe R; Nakao K; Yonenaka H; Hashimoto T; Kato N; Kumrungsee T; Yanaka N
[Ad] Endereço:Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima, Japan.
[Ti] Título:Time-course microarrays reveal early activation of the immune transcriptome in a choline-deficient mouse model of liver injury.
[So] Source:Life Sci;184:103-111, 2017 Sep 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Choline-deficient diet is extensively used as a model of nonalcoholic fatty liver disease (NAFLD). In this study, we explored genes in the liver for which the expression changed in response to the choline-deficient (CD) diet. MAIN METHODS: Male CD-1 mice were divided into two groups and fed a CD diet with or without 0.2% choline bitartrate for one or three weeks. Hepatic levels of choline metabolites were analyzed by using liquid chromatography mass spectrometry and hepatic gene expression profiles were examined by DNA microarray analysis. KEY FINDINGS: The CD diet lowered liver choline metabolites after one week and exacerbated fatty liver between one and three weeks. We identified >300 genes whose expression was significantly altered in the livers of mice after consumption of this CD diet for one week and showed that liver gene expression profiles could be classified into six distinct groups. This study showed that STAT1 and interferon-regulated genes was up-regulated after the CD diet consumption and that the Stat1 mRNA level was negatively correlated with liver phosphatidylcholine level. Stat1 mRNA expression was actually up-regulated in isolated hepatocytes from the mouse liver with the CD diet. SIGNIFICANCE: This study provides insight into the genomic effects of the CD diet through the Stat1 expression, which might be involved in NAFLD development.
[Mh] Termos MeSH primário: Colina/metabolismo
Perfilação da Expressão Gênica
Hepatócitos/metabolismo
Fígado/fisiopatologia
Hepatopatia Gordurosa não Alcoólica/fisiopatologia
[Mh] Termos MeSH secundário: Animais
Deficiência de Colina/complicações
Cromatografia Líquida
Modelos Animais de Doenças
Fígado/metabolismo
Masculino
Espectrometria de Massas
Camundongos
Camundongos Endogâmicos ICR
Hepatopatia Gordurosa não Alcoólica/genética
Análise de Sequência com Séries de Oligonucleotídeos
Fosfatidilcolinas/metabolismo
RNA Mensageiro
Fator de Transcrição STAT1/genética
Fatores de Tempo
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Phosphatidylcholines); 0 (RNA, Messenger); 0 (STAT1 Transcription Factor); 0 (STAT1 protein, human); N91BDP6H0X (Choline)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170815
[Lr] Data última revisão:
170815
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170717
[St] Status:MEDLINE


  6 / 1250 MEDLINE  
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[PMID]:28668831
[Au] Autor:Nakamura M; Suetsugu A; Hasegawa K; Matsumoto T; Aoki H; Kunisada T; Shimizu M; Saji S; Moriwaki H; Hoffman RM
[Ad] Endereço:Gifu University Graduate School of Medicine, Gifu, Japan.
[Ti] Título:Choline-Deficient-Diet-Induced Fatty Liver Is a Metastasis-Resistant Microenvironment.
[So] Source:Anticancer Res;37(7):3429-3434, 2017 07.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: Fatty liver disease is increasing in the developed and developing world. Liver metastasis from malignant lymphoma in the fatty liver is poorly understood. In a previous report, we developed color-coded imaging of the tumor microenvironment (TME) of the murine EL4-RFP malignant lymphoma during metastasis, including the lung. In the present report, we investigated the potential and microenvironment of the fatty liver induced by a choline-deficient diet as a metastatic site in this mouse lymphoma model. MATERIALS AND METHODS: C57BL/6-GFP transgenic mice were fed with a choline-deficient diet in order to establish a fatty liver model. EL4-RFP cells were injected in the spleen of normal mice and fatty-liver mice. Metastases in mice with fatty liver or normal liver were imaged with the Olympus SZX7 microscope and the Olympus FV1000 confocal microscope. RESULTS: Metastases of EL4-RFP were observed in the liver, ascites and bone marrow. Primary tumors were imaged in the spleen at the injection site. The fewest metastases were observed in the fatty liver. In addition, the fewest cancer-associated fibroblasts (CAFs) were observed in the fatty liver. CONCLUSION: The relative metastatic resistance of the fatty liver may be due to the reduced number of CAFs in the fatty livers. The mechanism of the effect of the choline-deficient diet is discussed.
[Mh] Termos MeSH primário: Deficiência de Colina/metabolismo
Deficiência de Colina/patologia
Colina/metabolismo
Dieta/efeitos adversos
Fígado Gorduroso/metabolismo
Microambiente Tumoral/fisiologia
[Mh] Termos MeSH secundário: Animais
Ascite/metabolismo
Ascite/patologia
Medula Óssea/metabolismo
Medula Óssea/patologia
Fibroblastos Associados a Câncer/metabolismo
Fibroblastos Associados a Câncer/patologia
Linhagem Celular Tumoral
Cor
Modelos Animais de Doenças
Fígado Gorduroso/patologia
Comportamento Alimentar/fisiologia
Fígado/metabolismo
Fígado/patologia
Neoplasias Hepáticas/metabolismo
Neoplasias Hepáticas/patologia
Linfoma/metabolismo
Linfoma/patologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Baço/metabolismo
Baço/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
N91BDP6H0X (Choline)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170906
[Lr] Data última revisão:
170906
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170703
[St] Status:MEDLINE


  7 / 1250 MEDLINE  
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[PMID]:28662136
[Au] Autor:Kanamori H; Nakade Y; Yamauchi T; Sakamoto K; Inoue T; Yamamoto T; Kobayashi Y; Ishii N; Ohashi T; Ito K; Sumida Y; Nakao H; Fukuzawa Y; Yoneda M
[Ad] Endereço:Division of Gastroenterology and Hepatology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi, Japan.
[Ti] Título:Influence of nicotine on choline-deficient, L-amino acid-defined diet-induced non-alcoholic steatohepatitis in rats.
[So] Source:PLoS One;12(6):e0180475, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nicotine, a major compound in cigarette smoke, decreases food intake and body weight gain in mammals; however, the influence of nicotine on the progression of non-alcoholic steatohepatitis (NASH) remains controversial. This study aimed to investigate the effect of nicotine on NASH in rat models. Male Wistar rats were fed choline-deficient, l-amino acid-defined (CDAA) diet and treated with nicotine or saline. Food intake, body weight gain, presence of hepatic steatosis, inflammation, and fibrosis were assessed 6 weeks after the rats were fed CDAA diet. Hepatic branch vagotomy was performed to elucidate the mechanism through which nicotine affected steatohepatitis. CDAA diet induced hepatic steatosis, inflammation, and fibrosis, as well as increased the expression of inflammation-related genes. Conversely, nicotine significantly attenuated food intake, body weight gain, and inhibited the CDAA-diet-induced hepatic steatosis, inflammation, and fibrosis, together with increased expression of inflammation-related genes. Hepatic branch vagotomy by itself decreased food intake, body weight gain, and attenuated the CDAA-diet-induced hepatic steatosis, but not inflammation. However, nicotine did not change the food intake, body weight gain, and CDAA diet-induced hepatic steatosis and inflammation in vagotomized rats. These results suggest that nicotine attenuates the CDAA-diet-induced hepatic steatosis and inflammation through the hepatic branch of the vagus nerve in rats.
[Mh] Termos MeSH primário: Aminoácidos/metabolismo
Deficiência de Colina/metabolismo
Nicotina/farmacologia
Hepatopatia Gordurosa não Alcoólica/metabolismo
[Mh] Termos MeSH secundário: Animais
Masculino
Ratos
Ratos Wistar
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 6M3C89ZY6R (Nicotine)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180475


  8 / 1250 MEDLINE  
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[PMID]:28632778
[Au] Autor:Kammoun HL; Allen TL; Henstridge DC; Kraakman MJ; Peijs L; Rose-John S; Febbraio MA
[Ad] Endereço:Cellular and Molecular Metabolism Laboratory, Baker Heart & Diabetes Institute, Melbourne, Australia.
[Ti] Título:Over-expressing the soluble gp130-Fc does not ameliorate methionine and choline deficient diet-induced non alcoholic steatohepatitis in mice.
[So] Source:PLoS One;12(6):e0179099, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Non-alcoholic steatohepatitis (NASH) is a liver disease with the potential to lead to cirrhosis and hepatocellular carcinoma. Interleukin-6 (IL-6) has been implicated in the pathogenesis of NASH, with the so-called IL-6 'trans-signaling' cascade being responsible for the pro-inflammatory actions of this cytokine. We aimed to block IL-6 'trans-signaling', using a transgenic mouse that overexpresses human soluble glycoprotein130 (sgp130Fc Tg mice) fed a commonly used dietary model of inducing NASH (methionine and choline deficient-diet; MCD diet) and hypothesized that markers of NASH would be ameliorated in such mice. Sgp130Fc Tg and littermate control mice were fed a MCD or control diet for 4 weeks. The MCD diet induced many hallmarks of NASH including hepatomegaly, steatosis, and liver inflammation. However, in contrast with other mouse models and, indeed, human NASH, the MCD diet model did not increase the mRNA or protein expression of IL-6. Not surprisingly, therefore, markers of MCD diet-induced NASH were unaffected by sgp130Fc transgenic expression. While the MCD diet model induces many pathophysiological markers of NASH, it does not induce increased IL-6 expression in the liver, a key hallmark of human NASH. We, therefore, caution the use of the MCD diet as a viable mouse model of NASH.
[Mh] Termos MeSH primário: Deficiência de Colina
Receptor gp130 de Citocina/administração & dosagem
Modelos Animais de Doenças
Inflamação/patologia
Interleucina-6/metabolismo
Metionina/deficiência
Hepatopatia Gordurosa não Alcoólica/patologia
[Mh] Termos MeSH secundário: Animais
Biomarcadores/metabolismo
Suplementos Nutricionais
Seres Humanos
Inflamação/induzido quimicamente
Inflamação/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Hepatopatia Gordurosa não Alcoólica/induzido quimicamente
Hepatopatia Gordurosa não Alcoólica/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Interleukin-6); 133483-10-0 (Cytokine Receptor gp130); AE28F7PNPL (Methionine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0179099


  9 / 1250 MEDLINE  
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[PMID]:28632732
[Au] Autor:Matsumoto K; Ichimura M; Tsuneyama K; Moritoki Y; Tsunashima H; Omagari K; Hara M; Yasuda I; Miyakawa H; Kikuchi K
[Ad] Endereço:Department of Gastroenterology, Teikyo University Mizonokuchi Hospital, Takatsu-ku, Kawasaki-city, Kanagawa, Japan.
[Ti] Título:Fructo-oligosaccharides and intestinal barrier function in a methionine-choline-deficient mouse model of nonalcoholic steatohepatitis.
[So] Source:PLoS One;12(6):e0175406, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Impairments in intestinal barrier function, epithelial mucins, and tight junction proteins have been reported to be associated with nonalcoholic steatohepatitis. Prebiotic fructo-oligosaccharides restore balance in the gastrointestinal microbiome. This study was conducted to determine the effects of dietary fructo-oligosaccharides on intestinal barrier function and steatohepatitis in methionine-choline-deficient mice. Three groups of 12-week-old male C57BL/6J mice were studied for 3 weeks; specifically, mice were fed a methionine-choline-deficient diet, a methionine-choline-deficient diet plus 5% fructo-oligosaccharides in water, or a normal control diet. Fecal bacteria, short-chain fatty acids, and immunoglobulin A (IgA) levels were investigated. Histological and immunohistochemical examinations were performed using mice livers for CD14 and Toll-like receptor-4 (TLR4) expression and intestinal tissue samples for IgA and zonula occludens-1 expression in epithelial tight junctions. The methionine-choline-deficient mice administered 5% fructo-oligosaccharides maintained a normal gastrointestinal microbiome, whereas methionine-choline-deficient mice without prebiotic supplementation displayed increases in Clostridium cluster XI and subcluster XIVa populations and a reduction in Lactobacillales spp. counts. Methionine-choline-deficient mice given 5% fructo-oligosaccharides exhibited significantly decreased hepatic steatosis (p = 0.003), decreased liver inflammation (p = 0.005), a decreased proportion of CD14-positive Kupffer cells (p = 0.01), decreased expression of TLR4 (p = 0.04), and increases in fecal short-chain fatty acid and IgA concentrations (p < 0.04) compared with the findings in methionine-choline-deficient mice that were not administered this prebiotic. This study illustrated that in the methionine-choline-deficient mouse model, dietary fructo-oligosaccharides can restore normal gastrointestinal microflora and normal intestinal epithelial barrier function, and decrease steatohepatitis. The findings support the role of prebiotics, such as fructo-oligosaccharides, in maintaining a normal gastrointestinal microbiome; they also support the need for further studies on preventing or treating nonalcoholic steatohepatitis using dietary fructo-oligosaccharides.
[Mh] Termos MeSH primário: Deficiência de Colina
Modelos Animais de Doenças
Intestinos/fisiologia
Metionina/deficiência
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico
Oligossacarídeos/administração & dosagem
[Mh] Termos MeSH secundário: Animais
Suplementos Nutricionais
Intestinos/efeitos dos fármacos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Hepatopatia Gordurosa não Alcoólica/induzido quimicamente
Hepatopatia Gordurosa não Alcoólica/patologia
Prebióticos/administração & dosagem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Oligosaccharides); 0 (Prebiotics); 0 (fructooligosaccharide); AE28F7PNPL (Methionine)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170621
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175406


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[PMID]:28414763
[Au] Autor:Wankhade UD; Zhong Y; Kang P; Alfaro M; Chintapalli SV; Thakali KM; Shankar K
[Ad] Endereço:Arkansas Children's Nutrition Center, Little Rock, Arkansas, United States of America.
[Ti] Título:Enhanced offspring predisposition to steatohepatitis with maternal high-fat diet is associated with epigenetic and microbiome alterations.
[So] Source:PLoS One;12(4):e0175675, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity associated with obesity and a precursor to steatohepatitis. However, the contributions of gestational and early life influences on development of NAFLD and NASH remain poorly appreciated. METHODS: Two independent studies were performed to examine whether maternal over-nutrition via exposure to high fat diet (HFD) leads to exacerbated hepatic responses to post-natal HFD and methionine choline deficient (MCD) diets in the offspring. Offspring of both control diet- and HFD-fed dams were weaned onto control and HFD, creating four groups. RESULTS: When compared to their control diet-fed littermates, offspring of HF-dams weaned onto HFD gained greater body weight; had increased relative liver weight and showed hepatic steatosis and inflammation. Similarly, this group revealed significantly greater immune response and pro-fibrogenic gene expression via RNA-seq. In parallel, 7-8 week old offspring were challenged with either control or MCD diets for 3 weeks. Responses to MCD diets were also exacerbated due to maternal HFD as seen by gene expression of classical pro-fibrogenic genes. Quantitative genome-scale DNA methylation analysis of over 1 million CpGs showed persistent epigenetic changes in key genes in tissue development and metabolism (Fgf21, Ppargc1ß) with maternal HFD and in cell adhesion and communication (VWF, Ephb2) in the combination of maternal HFD and offspring MCD diets. Maternal HFD also influenced gut microbiome profiles in offspring leading to a decrease in α-diversity. Linear regression analysis revealed association between serum ALT levels and Coprococcus, Coriobacteriacae, Helicobacterioceae and Allobaculum. CONCLUSION: Our findings indicate that maternal HFD detrimentally alters epigenetic and gut microbiome pathways to favor development of fatty liver disease and its progressive sequelae.
[Mh] Termos MeSH primário: Dieta Hiperlipídica/efeitos adversos
Hepatopatia Gordurosa não Alcoólica/etiologia
Efeitos Tardios da Exposição Pré-Natal/etiologia
[Mh] Termos MeSH secundário: Animais
Colina/administração & dosagem
Deficiência de Colina/complicações
Metilação de DNA
Modelos Animais de Doenças
Epigênese Genética
Feminino
Microbioma Gastrointestinal/genética
Perfilação da Expressão Gênica
Fígado/metabolismo
Masculino
Fenômenos Fisiológicos da Nutrição Materna
Metionina/administração & dosagem
Metionina/deficiência
Camundongos
Camundongos Endogâmicos C57BL
Hepatopatia Gordurosa não Alcoólica/genética
Hepatopatia Gordurosa não Alcoólica/microbiologia
Hipernutrição/complicações
Gravidez
Efeitos Tardios da Exposição Pré-Natal/genética
Efeitos Tardios da Exposição Pré-Natal/microbiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
AE28F7PNPL (Methionine); N91BDP6H0X (Choline)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170418
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0175675



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