{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:55:25Z","timestamp":1790740525844,"version":"4.1.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","license":[{"start":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T00:00:00Z","timestamp":1500508800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Communications"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:p>Tumor necrosis factor\u2010related apoptosis\u2010inducing ligand (TRAIL) and its cognate receptor(s) are up\u2010regulated in human and murine nonalcoholic steatohepatitis (NASH); however, the consequence of this enhanced expression on NASH pathogenesis remains unclear. TRAIL may either accentuate liver injury by promoting hepatic steatosis and inflammation or it may mitigate the disease process by improving systemic insulin resistance and averting hepatic fibrosis. Herein, we investigated the role of TRAIL in an obesity\u2010induced murine model of NASH. C57BL\/6 wild\u2010type mice and <jats:italic toggle=\"yes\">Trail<\/jats:italic>\n                           <jats:sup>\u2013\/\u2013<\/jats:sup> mice were placed on a 20\u2010week standard chow or a high\u2010fat, high\u2010fructose, and high\u2010cholesterol (FFC) diet, which induces obesity, insulin resistance, and NASH. Metabolic phenotype, liver injury, inflammation and fibrosis, and adipose tissue homeostasis were examined. FFC diet\u2010fed <jats:italic toggle=\"yes\">Trail<\/jats:italic>\n                           <jats:sup>\u2013\/\u2013<\/jats:sup> mice displayed no difference in weight gain and metabolic profile when compared to wild\u2010type mice on the same diet. All FFC\u2010fed mice developed significant hepatic steatosis, which was attenuated in <jats:italic toggle=\"yes\">Trail<\/jats:italic>\n                           <jats:sup>\u2013\/\u2013<\/jats:sup> mice. TRAIL deficiency also significantly decreased FFC diet\u2010induced liver injury as manifested by reduced serum alanine aminotransferase values, hepatic terminal deoxynucleotidyl transferase\u2010mediated deoxyuridine triphosphate nick\u2010end labeling\u2010positive cells, and macrophage\u2010associated inflammation. FFC diet\u2010associated hepatic stellate cell activation and hepatic collagen deposition were also abrogated in <jats:italic toggle=\"yes\">Trail<\/jats:italic>\n                           <jats:sup>\u2013\/\u2013<\/jats:sup> mice. In contrast to the liver, TRAIL deletion did not improve FFC diet\u2010induced adipose tissue injury and inflammation and actually aggravated insulin resistance. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: NASH pathogenesis may be dissociated from other features of the metabolic syndrome, and liver\u2010targeted inhibition of TRAIL signaling may be salutary. (<jats:italic toggle=\"yes\">Hepatology Communications<\/jats:italic> 2017;1:648\u2013662)<\/jats:p>","DOI":"10.1002\/hep4.1069","type":"journal-article","created":{"date-parts":[[2017,7,20]],"date-time":"2017-07-20T13:34:34Z","timestamp":1500557674000},"page":"648-662","source":"Crossref","is-referenced-by-count":44,"title":["TRAIL deletion prevents liver inflammation but not adipose tissue inflammation during murine diet\u2010induced obesity"],"prefix":"10.1097","volume":"1","author":[{"given":"Petra","family":"Hirsova","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Weng","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warda","family":"Salim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven F.","family":"Bronk","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Urology,University of Minnesota,Minneapolis,MN"},{"name":"Microbiology,Immunology, and Cancer Biology Graduate Program, University of Minnesota,Minneapolis,MN"},{"name":"Center for Immunology,University of Minnesota,Minneapolis,MN"},{"name":"Masonic Cancer Center,University of Minnesota,Minneapolis,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samar H.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"},{"name":"Division of Pediatric Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory J.","family":"Gores","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2017,7,20]]},"reference":[{"key":"hep41069-bib-0001-20240114","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1001\/jama.2015.5370","article-title":"Nonalcoholic fatty liver disease: a systematic review","volume":"313","year":"2015","journal-title":"JAMA"},{"key":"hep41069-bib-0002-20240114","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1002\/hep.28524","article-title":"The globalization of nonalcoholic fatty liver disease: prevalence and impact on world 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Opposing unfolded\u2010protein\u2010response signals converge on death receptor 5 to control apoptosis","volume":"345","year":"2014","journal-title":"Science"},{"key":"hep41069-bib-0038-20240114","doi-asserted-by":"crossref","first-page":"3157","DOI":"10.1007\/s00125-011-2308-0","article-title":"TNF\u2010related apoptosis\u2010inducing ligand (TRAIL) protects against diabetes and atherosclerosis in Apoe\u2013\/\u2013 mice","volume":"54","year":"2011","journal-title":"Diabetologia"}],"container-title":["Hepatology Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep4.1069","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/02009842-201709000-00008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,14]],"date-time":"2024-01-14T16:03:37Z","timestamp":1705248217000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/02009842-201709000-00008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,20]]},"references-count":38,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2017]]}},"URL":"https:\/\/doi.org\/10.1002\/hep4.1069","relation":{},"ISSN":["2471-254X","2471-254X"],"issn-type":[{"value":"2471-254X","type":"print"},{"value":"2471-254X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,20]]}}}