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{"title"=>"High Fat Diet Induces Liver Steatosis and Early Dysregulation of Iron Metabolism in Rats", "type"=>"journal", "authors"=>[{"first_name"=>"Rosaria", "last_name"=>"Meli", "scopus_author_id"=>"7006095900"}, {"first_name"=>"Giuseppina", "last_name"=>"Mattace Raso", "scopus_author_id"=>"7006210258"}, {"first_name"=>"Carlo", "last_name"=>"Irace", "scopus_author_id"=>"6701512461"}, {"first_name"=>"Raffaele", "last_name"=>"Simeoli", "scopus_author_id"=>"37112972900"}, {"first_name"=>"Antonio", "last_name"=>"Di Pascale", "scopus_author_id"=>"26653935900"}, {"first_name"=>"Orlando", "last_name"=>"Paciello", "scopus_author_id"=>"57200386585"}, {"first_name"=>"Teresa Bruna", "last_name"=>"Pagano", "scopus_author_id"=>"55771124100"}, {"first_name"=>"Antonio", "last_name"=>"Calignano", "scopus_author_id"=>"7003942979"}, {"first_name"=>"Alfredo", "last_name"=>"Colonna", "scopus_author_id"=>"7005724970"}, {"first_name"=>"Rita", "last_name"=>"Santamaria", "scopus_author_id"=>"24746858000"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"23805238", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0066570", "pui"=>"369158152", "isbn"=>"1932-6203 (Electronic)\\n1932-6203 (Linking)", "scopus"=>"2-s2.0-84879263200", "sgr"=>"84879263200"}, "id"=>"a44b414f-8544-3bed-b862-ae41a8d53f72", "abstract"=>"This paper is dedicated to the memory of our wonderful colleague Professor Alfredo Colonna, who passed away the same day of its acceptance. Fatty liver accumulation, inflammatory process and insulin resistance appear to be crucial in non-alcoholic fatty liver disease (NAFLD), nevertheless emerging findings pointed an important role also for iron overload. Here, we investigate the molecular mechanisms of hepatic iron metabolism in the onset of steatosis to understand whether its impairment could be an early event of liver inflammatory injury. Rats were fed with control diet or high fat diet (HFD) for 5 or 8 weeks, after which liver morphology, serum lipid profile, transaminases levels and hepatic iron content (HIC), were evaluated. In liver of HFD fed animals an increased time-dependent activity of iron regulatory protein 1 (IRP1) was evidenced, associated with the increase in transferrin receptor-1 (TfR1) expression and ferritin down-regulation. Moreover, ferroportin (FPN-1), the main protein involved in iron export, was down-regulated accordingly with hepcidin increase. These findings were indicative of an increased iron content into hepatocytes, which leads to an increase of harmful free-iron also related to the reduction of hepatic ferritin content. The progressive inflammatory damage was evidenced by the increase of hepatic TNF-α, IL-6 and leptin, in parallel to increased iron content and oxidative stress. The major finding that emerged of this study is the impairment of iron homeostasis in the ongoing and sustaining of liver steatosis, suggesting a strong link between iron metabolism unbalance, inflammatory damage and progression of disease.", "link"=>"http://www.mendeley.com/research/high-fat-diet-induces-liver-steatosis-early-dysregulation-iron-metabolism-rats", "reader_count"=>32, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Librarian"=>1, "Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>4, "Student > Bachelor"=>3}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Librarian"=>1, "Researcher"=>6, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>8, "Student > Postgraduate"=>1, "Student > Master"=>6, "Other"=>4, "Student > Bachelor"=>3}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>13, "Sports and Recreations"=>1, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Social Sciences"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>13}, "Social Sciences"=>{"Social Sciences"=>2}, "Sports and Recreations"=>{"Sports and Recreations"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"Republic of Singapore"=>1, "Belgium"=>1}, "group_count"=>1}

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• http://doi.org/10.3748/wjg.v22.i32.7353
• http://doi.org/10.15789/1563-0625-2018-5-639-646
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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1096825"], "description"=>"<p>(A) IRP1 RNA-binding activity in liver after control (CD) and high fat (HFD) diet for 5 or 8 weeks. Immunoblots showed IRP1 (B), TfR1 (C), and ferritin (D) protein levels in extracts from liver of rats after CD and HFD. The results of experiments were plotted in a bar graph as percent of the control. GAPDH was used as internal control. Shown are the means ± S.E.M. of all bands plotted in a bar graph compared to control animals. ***P<0.001 vs CD; #P<0.05;##P<0.01 vs HFD 5 weeks.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "homeostasis", "Biochemistry", "metabolism", "immunology", "Immune system", "cytokines", "immunity", "inflammation", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Cellular stress responses", "Clinical immunology", "Gastroenterology and hepatology", "Liver diseases", "Nonalcoholic steatohepatitis", "Metabolic disorders", "nutrition", "modulation", "proteins"], "article_id"=>728064, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rosaria Meli", "Giuseppina Mattace Raso", "Carlo Irace", "Raffaele Simeoli", "Antonio Di Pascale", "Orlando Paciello", "Teresa Bruna Pagano", "Antonio Calignano", "Alfredo Colonna", "Rita Santamaria"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066570.g005", "stats"=>{"downloads"=>0, "page_views"=>3, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Time_dependent_modulation_of_iron_metabolism_related_proteins_by_HFD_/728064", "title"=>"Time dependent modulation of iron metabolism related proteins by HFD.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 02:05:37"}
• {"files"=>["https://ndownloader.figshare.com/files/1096823"], "description"=>"<p>Tissue oxidative stress was evaluated after 5 or 8 weeks feeding with HFD by protein nitrotyrosylation (A) and MDA measurament (B). The displayed data are mean values ± SEM of rats on CD or HFD. **P<0.01, and ***P<0.001 vs CD; ##P<0.01 vs HFD 5 weeks.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "homeostasis", "Biochemistry", "metabolism", "immunology", "Immune system", "cytokines", "immunity", "inflammation", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Cellular stress responses", "Clinical immunology", "Gastroenterology and hepatology", "Liver diseases", "Nonalcoholic steatohepatitis", "Metabolic disorders", "nutrition", "causes", "oxidative"], "article_id"=>728062, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rosaria Meli", "Giuseppina Mattace Raso", "Carlo Irace", "Raffaele Simeoli", "Antonio Di Pascale", "Orlando Paciello", "Teresa Bruna Pagano", "Antonio Calignano", "Alfredo Colonna", "Rita Santamaria"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066570.g003", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HFD_causes_oxidative_stress_in_liver_/728062", "title"=>"HFD causes oxidative stress in liver.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 02:05:37"}
• {"files"=>["https://ndownloader.figshare.com/files/1096822"], "description"=>"<p>Tissue iron content was measured by atomic absorption (A) and Perls’blue staining (B) in liver of control diet (CD) or HFD fed rats (5 or 8 weeks). Micrographs in panels are representative pictures with magnification 400 X. The displayed data are mean values ± SEM of rats on CD or HFD. *P<0.05 vs CD.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "homeostasis", "Biochemistry", "metabolism", "immunology", "Immune system", "cytokines", "immunity", "inflammation", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Cellular stress responses", "Clinical immunology", "Gastroenterology and hepatology", "Liver diseases", "Nonalcoholic steatohepatitis", "Metabolic disorders", "nutrition", "causes", "overload"], "article_id"=>728061, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rosaria Meli", "Giuseppina Mattace Raso", "Carlo Irace", "Raffaele Simeoli", "Antonio Di Pascale", "Orlando Paciello", "Teresa Bruna Pagano", "Antonio Calignano", "Alfredo Colonna", "Rita Santamaria"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066570.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HFD_causes_iron_overload_in_liver_/728061", "title"=>"HFD causes iron overload in liver.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 02:05:37"}
• {"files"=>["https://ndownloader.figshare.com/files/1096818"], "description"=>"<p>Liver sections were stained with (<b>A</b>) hematoxylin-eosin or (<b>B</b>) Oil red O. Micrographs in both panels are representative pictures with magnification 400 X. (<b>C</b>) Quantitative analysis of liver TGL content obtained from all animals is expressed as mg/dl in 500 mg tissue. (<b>D</b>) Real time-PCR of TNF-α mRNA is shown. **P<0.01 and ***P<0.001 vs CD; #P<0.05 vs HFD 5 weeks.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "homeostasis", "Biochemistry", "metabolism", "immunology", "Immune system", "cytokines", "immunity", "inflammation", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Cellular stress responses", "Clinical immunology", "Gastroenterology and hepatology", "Liver diseases", "Nonalcoholic steatohepatitis", "Metabolic disorders", "nutrition", "lipid", "rats"], "article_id"=>728057, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rosaria Meli", "Giuseppina Mattace Raso", "Carlo Irace", "Raffaele Simeoli", "Antonio Di Pascale", "Orlando Paciello", "Teresa Bruna Pagano", "Antonio Calignano", "Alfredo Colonna", "Rita Santamaria"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066570.g001", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Histological_analysis_lipid_and_TNF_945_content_in_liver_of_young_rats_on_control_CD_and_high_fat_HFD_diet_for_5_or_8_weeks_/728057", "title"=>"Histological analysis, lipid and TNF-α content in liver of young rats on control (CD) and high fat (HFD) diet for 5 or 8 weeks.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 02:05:37"}
• {"files"=>["https://ndownloader.figshare.com/files/1096826"], "description"=>"<p>Values are means ± S.E.M of at least six animals.</p>*<p>P<0.05,</p>**<p>P<0.01;</p>***<p>P<0.001 vs CD.</p>#<p>P<0.05.</p>##<p>P<0.01, and ^###P<0.001 vs HFD 5 weeks.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "homeostasis", "Biochemistry", "metabolism", "immunology", "Immune system", "cytokines", "immunity", "inflammation", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Cellular stress responses", "Clinical immunology", "Gastroenterology and hepatology", "Liver diseases", "Nonalcoholic steatohepatitis", "Metabolic disorders", "nutrition", "serum", "rats", "fed"], "article_id"=>728065, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rosaria Meli", "Giuseppina Mattace Raso", "Carlo Irace", "Raffaele Simeoli", "Antonio Di Pascale", "Orlando Paciello", "Teresa Bruna Pagano", "Antonio Calignano", "Alfredo Colonna", "Rita Santamaria"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066570.t001", "stats"=>{"downloads"=>0, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_serum_parameters_of_rats_fed_with_control_CD_and_high_fat_HFD_diet_for_5_or_8_weeks_/728065", "title"=>"Changes in serum parameters of rats fed with control (CD) and high fat (HFD) diet for 5 or 8 weeks.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-21 02:05:37"}
• {"files"=>["https://ndownloader.figshare.com/files/1096824"], "description"=>"<p>(A) Real time-PCR of IL-6, (B) c/EBPα and (C) hepcidin mRNA in liver extracts from CD and HFD fed rats for 5 or 8 weeks. (D) Immunoblot of ferroportin (FPN-1) is shown. The bands were densitometrically quantified and plotted. (E) Real time-PCR of hepatic leptin mRNA and (F) serum leptin level, expressed as pg/ml, are shown. *P<0.05; **P<0.01, and ***P<0.001 vs CD; ##P<0.01 vs HFD 5 weeks.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "homeostasis", "Biochemistry", "metabolism", "immunology", "Immune system", "cytokines", "immunity", "inflammation", "Model organisms", "Animal models", "rat", "Molecular cell biology", "Cellular stress responses", "Clinical immunology", "Gastroenterology and hepatology", "Liver diseases", "Nonalcoholic steatohepatitis", "Metabolic disorders", "nutrition", "pro-inflammatory", "markers", "time-dependently", "fpn-1"], "article_id"=>728063, "categories"=>["Medicine", "Biological Sciences"], "users"=>["Rosaria Meli", "Giuseppina Mattace Raso", "Carlo Irace", "Raffaele Simeoli", "Antonio Di Pascale", "Orlando Paciello", "Teresa Bruna Pagano", "Antonio Calignano", "Alfredo Colonna", "Rita Santamaria"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066570.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_HFD_induces_pro_inflammatory_markers_and_affects_time_dependently_c_EBP_945_hepcidin_and_FPN_1_expression_/728063", "title"=>"HFD induces pro-inflammatory markers and affects time-dependently c/EBPα, hepcidin, and FPN-1 expression.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-21 02:05:37"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Immunology", "average_usage"=>[266, 466, 591, 701, 799, 887, 982, 1067, 1155, 1237, 1317, 1395, 1458]}, {"subject_area"=>"/Medicine and health sciences/Immunology", "average_usage"=>[262, 463, 587, 693, 790, 882, 965, 1051, 1135, 1218, 1300, 1376, 1438]}, {"subject_area"=>"/Medicine and health sciences/Inflammatory diseases", "average_usage"=>[255, 445, 583, 697, 792, 882, 971, 1045, 1128, 1221, 1291, 1409, 1462, 1534]}, {"subject_area"=>"/Medicine and health sciences/Nutrition", "average_usage"=>[273, 476, 611, 714, 821, 911, 1005, 1103, 1201, 1287, 1388, 1478, 1557]}, {"subject_area"=>"/Physical sciences", "average_usage"=>[254, 431, 547, 651, 748, 842, 932, 1017, 1098, 1178, 1259, 1336, 1404]}]}

F1000Prime