{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:45:45Z","timestamp":1791276345754,"version":"4.1.0"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2014,5,22]],"date-time":"2014-05-22T00:00:00Z","timestamp":1400716800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0097136","type":"journal-article","created":{"date-parts":[[2014,5,22]],"date-time":"2014-05-22T16:40:19Z","timestamp":1400776819000},"page":"e97136","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":92,"title":["HCC Development Is Associated to Peripheral Insulin Resistance in a Mouse Model of NASH"],"prefix":"10.1371","volume":"9","author":[{"given":"Samuele","family":"De Minicis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Agostinelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Rychlicki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian Pio","family":"Sorice","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Saccomanno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cinzia","family":"Candelaresi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Giaccari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Trozzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Pierantonelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Mingarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Marzioni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Muscogiuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melania","family":"Gaggini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Benedetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amalia","family":"Gastaldelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Guido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Svegliati-Baroni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,5,22]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1056\/NEJMra1001683","article-title":"Hepatocellular carcinoma","volume":"365","author":"HB El-Serag","year":"2011","journal-title":"N Engl J Med"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.cld.2009.07.007","article-title":"NASH and HCC","volume":"13","author":"JM Page","year":"2009","journal-title":"Clin Liver Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.2337\/diabetes.50.8.1844","article-title":"Nonalcoholic fatty liver disease: a feature of the metabolic syndrome","volume":"50","author":"G Marchesini","year":"2001","journal-title":"Diabetes"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1053\/j.gastro.2005.05.041","article-title":"Natural history of NAFLD: remarkably benign in the absence of cirrhosis","volume":"129","author":"CP Day","year":"2005","journal-title":"Gastroenterology"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1218","DOI":"10.1016\/j.jhep.2012.12.003","article-title":"A 360-degree overview of paediatric NAFLD: recent insights","volume":"58","author":"V Nobili","year":"2013","journal-title":"J Hepatol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"5239","DOI":"10.2174\/1381612811319290006","article-title":"From NAFLD to NASH and HCC: pathogenetic mechanisms and therapeutic insights","volume":"19","author":"S De Minicis","year":"2013","journal-title":"Curr Pharm Des"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1055\/s-2001-12932","article-title":"Animal models of steatosis","volume":"21","author":"A Koteish","year":"2001","journal-title":"Semin Liver Dis"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1136\/gut.2006.107946","article-title":"Post-load insulin resistance is an independent predictor of hepatic fibrosis in virus C chronic hepatitis and in non-alcoholic fatty liver disease","volume":"56","author":"G Svegliati-Baroni","year":"2007","journal-title":"Gut"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.dld.2010.01.016","article-title":"From the metabolic syndrome to NAFLD or vice versa?","volume":"42","author":"E Vanni","year":"2010","journal-title":"Dig Liver Dis"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1172\/JCI115583","article-title":"Predominant role of gluconeogenesis in the hepatic glycogen repletion of diabetic rats","volume":"89","author":"A Giaccari","year":"1992","journal-title":"J Clin Invest"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1007\/BF00400719","article-title":"In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: possible relevance to the maladaptive responses to chronic hyperglycaemia","volume":"38","author":"A Giaccari","year":"1995","journal-title":"Diabetologia"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1111\/j.1478-3231.2011.02462.x","article-title":"Glucagon-like peptide-1 receptor activation stimulates hepatic lipid oxidation and restores hepatic signalling alteration induced by a high-fat diet in nonalcoholic steatohepatitis","volume":"31","author":"G Svegliati-Baroni","year":"2011","journal-title":"Liver Int"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/hep.20701","article-title":"Design and validation of a histological scoring system for nonalcoholic fatty liver disease","volume":"41","author":"DE Kleiner","year":"2005","journal-title":"Hepatology"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"De Minicis S, Candelaresi C, Agostinelli L, Taffetani S, Saccomanno S, <etal>et al<\/etal>.. (2012) Endoplasmic Reticulum stress induces hepatic stellate cell apoptosis and contributes to fibrosis resolution. Liver Int.","DOI":"10.1111\/j.1478-3231.2012.02860.x"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1016\/j.jhep.2005.10.032","article-title":"Estrogens maintain bile duct mass and reduce apoptosis after biliodigestive anastomosis in bile duct ligated rats","volume":"44","author":"G Svegliati-Baroni","year":"2006","journal-title":"J Hepatol"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1172\/JCI200422422","article-title":"Molecular mediators of hepatic steatosis and liver injury","volume":"114","author":"JD Browning","year":"2004","journal-title":"J Clin Invest"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1053\/j.gastro.2010.12.006","article-title":"Increased lipogenesis, induced by AKT-mTORC1-RPS6 signaling, promotes development of human hepatocellular carcinoma","volume":"140","author":"DF Calvisi","year":"2011","journal-title":"Gastroenterology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/hep.21467","article-title":"Transcriptome classification of HCC is related to gene alterations and to new therapeutic targets","volume":"45","author":"S Boyault","year":"2007","journal-title":"Hepatology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/hep.24199","article-title":"Management of hepatocellular carcinoma: an update","volume":"53","author":"J Bruix","year":"2011","journal-title":"Hepatology"},{"key":"ref20","first-page":"5055","article-title":"Up-regulation of glypican-3 in human hepatocellular carcinoma","volume":"30","author":"M Suzuki","year":"2010","journal-title":"Anticancer Res"},{"key":"ref21","first-page":"108","article-title":"Insulin resistance and necroinflammation drives ductular reaction and epithelial-mesenchymal transition in chronic hepatitis C. Gut","volume":"60","author":"G Svegliati-Baroni","year":"2011"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.molmed.2007.12.003","article-title":"Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis","volume":"14","author":"F Marra","year":"2008","journal-title":"Trends Mol Med"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Kodama Y, Kisseleva T, Iwaisako K, Miura K, Taura K, <etal>et al<\/etal>.. (2009) c-Jun N-terminal kinase-1 from hematopoietic cells mediates progression from hepatic steatosis to steatohepatitis and fibrosis in mice. Gastroenterology 137: 1467\u20131477 e1465.","DOI":"10.1053\/j.gastro.2009.06.045"},{"key":"ref24","unstructured":"Miura K, Kodama Y, Inokuchi S, Schnabl B, Aoyama T, <etal>et al<\/etal>.. (2010) Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1beta in mice. Gastroenterology 139: 323\u2013334 e327."},{"key":"ref25","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.jhep.2010.11.028","article-title":"Impact of artificial sunlight therapy on the progress of non-alcoholic fatty liver disease in rats","volume":"55","author":"T Nakano","year":"2011","journal-title":"J Hepatol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"6497","DOI":"10.1128\/MCB.00679-07","article-title":"Peripheral disruption of the Grb10 gene enhances insulin signaling and sensitivity in vivo","volume":"27","author":"L Wang","year":"2007","journal-title":"Mol Cell Biol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"976","DOI":"10.1053\/j.gastro.2010.11.049","article-title":"Association between composition of the human gastrointestinal microbiome and development of fatty liver with choline deficiency","volume":"140","author":"MD Spencer","year":"2011","journal-title":"Gastroenterology"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"e10883","DOI":"10.1371\/journal.pone.0010883","article-title":"alpha-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population","volume":"5","author":"WE Gall","year":"2010","journal-title":"PLoS One"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Ferrannini E, Natali A, Camastra S, Nannipieri M, Mari A, <etal>et al<\/etal>.. (2012) Early Metabolic Markers of the Development of Dysglycemia and Type 2 Diabetes and Their Physiological Significance. Diabetes.","DOI":"10.2337\/db12-0707"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"S60","DOI":"10.1016\/S0168-8227(11)70015-8","article-title":"Role of beta-cell dysfunction, ectopic fat accumulation and insulin resistance in the pathogenesis of type 2 diabetes mellitus","volume":"93","author":"A Gastaldelli","year":"2011","journal-title":"Diabetes Res Clin Pract"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.2337\/dc12-1760","article-title":"Circulating lysophosphatidylcholines are markers of a metabolically benign nonalcoholic fatty liver","volume":"36","author":"R Lehmann","year":"2013","journal-title":"Diabetes Care"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"De Minicis S, Rychlicki C, Agostinelli L, Saccomanno S, Candelaresi C, <etal>et al<\/etal>.. (2013) Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice. Hepatology.","DOI":"10.1016\/S0168-8278(13)61252-0"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature10809","article-title":"Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity","volume":"482","author":"J Henao-Mejia","year":"2012","journal-title":"Nature"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1007\/s00125-005-1682-x","article-title":"Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms","volume":"48","author":"E Bugianesi","year":"2005","journal-title":"Diabetologia"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.prostaglandins.2011.10.002","article-title":"Epoxyeicosatrienoic acids and heme oxygenase-1 interaction attenuates diabetes and metabolic syndrome complications","volume":"97","author":"A Burgess","year":"2012","journal-title":"Prostaglandins Other Lipid Mediat"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.2337\/diabetes.50.8.1807","article-title":"Effect of physiological hyperinsulinemia on gluconeogenesis in nondiabetic subjects and in type 2 diabetic patients","volume":"50","author":"A Gastaldelli","year":"2001","journal-title":"Diabetes"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1002\/hep.26698","article-title":"Transforming growth factor beta signaling in hepatocytes participates in steatohepatitis through regulation of cell death and lipid metabolism in mice","volume":"59","author":"L Yang","year":"2014","journal-title":"Hepatology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1749-6632.2009.03704.x","article-title":"Inflammation and liver cancer: new molecular links","volume":"1155","author":"C Berasain","year":"2009","journal-title":"Ann N Y Acad Sci"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1038\/nrc1934","article-title":"Hepatocellular carcinoma pathogenesis: from genes to environment","volume":"6","author":"PA Farazi","year":"2006","journal-title":"Nat Rev Cancer"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1053\/j.gastro.2008.03.003","article-title":"Mechanisms of hepatic fibrogenesis","volume":"134","author":"SL Friedman","year":"2008","journal-title":"Gastroenterology"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"S45","DOI":"10.1002\/hep.20969","article-title":"Liver regeneration","volume":"43","author":"N Fausto","year":"2006","journal-title":"Hepatology"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1016\/j.jhep.2012.03.035","article-title":"Inflammasomes in liver diseases","volume":"57","author":"G Szabo","year":"2012","journal-title":"J Hepatol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1053\/j.gastro.2012.09.008","article-title":"Sterile inflammation in the liver","volume":"143","author":"P Kubes","year":"2012","journal-title":"Gastroenterology"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.jhep.2011.09.020","article-title":"Obesity, inflammation, and liver cancer","volume":"56","author":"B Sun","year":"2012","journal-title":"J Hepatol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"2490","DOI":"10.1002\/cncr.22701","article-title":"Hepatic steatosis is associated with increased frequency of hepatocellular carcinoma in patients with hepatitis C-related cirrhosis","volume":"109","author":"JR Pekow","year":"2007","journal-title":"Cancer"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/nrd2781","article-title":"Is NF-kappaB a good target for cancer therapy? Hopes and pitfalls","volume":"8","author":"V Baud","year":"2009","journal-title":"Nat Rev Drug Discov"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/j.1349-7006.2002.tb01250.x","article-title":"Development of hepatocellular adenomas and carcinomas associated with fibrosis in C57BL\/6J male mice given a choline-deficient, L-amino acid-defined diet","volume":"93","author":"A Denda","year":"2002","journal-title":"Jpn J Cancer Res"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.cytogfr.2008.01.005","article-title":"IGF2: epigenetic regulation and role in development and disease","volume":"19","author":"W Chao","year":"2008","journal-title":"Cytokine Growth Factor Rev"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.3748\/wjg.v16.i37.4627","article-title":"PTEN in liver diseases and cancer","volume":"16","author":"M Peyrou","year":"2010","journal-title":"World J Gastroenterol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/S1665-2681(19)31848-4","article-title":"PTEN at the crossroad of metabolic diseases and cancer in the liver","volume":"7","author":"M Vinciguerra","year":"2008","journal-title":"Ann Hepatol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0097136","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,10]],"date-time":"2019-08-10T15:16:57Z","timestamp":1565450217000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0097136"}},"subtitle":[],"editor":[{"given":"Birke","family":"Bartosch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,5,22]]},"references-count":50,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2014,5,22]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0097136","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,5,22]]}}}