{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T14:16:49Z","timestamp":1776867409945,"version":"3.51.2"},"reference-count":37,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T00:00:00Z","timestamp":1604620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PRIN 2009 \u2010 prot. 2009YNERCE"],"award-info":[{"award-number":["PRIN 2009 \u2010 prot. 2009YNERCE"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["_002"],"award-info":[{"award-number":["_002"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["FIRB 2010 \u2010 prot. RBAP10MY35_001"],"award-info":[{"award-number":["FIRB 2010 \u2010 prot. RBAP10MY35_001"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Liver X receptors (LXRs) exert anti\u2010inflammatory effects even though their hepatic activation is associated with hypertriglyceridemia and hepatic steatosis. Selective induction of LXRs in the gut might provide protective signal(s) in the aberrant wound healing response that induces fibrosis during chronic liver injury, without hypertriglyceridemic and steatogenic effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice with intestinal constitutive LXR\u03b1 activation (iVP16\u2010LXR\u03b1) were exposed to intraperitoneal injection of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) for 8\u00a0weeks, and in vitro cell models were used to evaluate the beneficial effect of high\u2010density lipoproteins (HDL).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After CCl<jats:sub>4<\/jats:sub> treatment, the iVP16\u2010LXR\u03b1 phenotype showed reduced M1 macrophage infiltration, increased expression M2 macrophage markers, and lower expression of hepatic pro\u2010inflammatory genes. This anti\u2010inflammatory effect in the liver was also associated with decreased expression of hepatic oxidative stress genes and reduced expression of fibrosis markers. iVP16\u2010LXR\u03b1 exhibited increased reverse cholesterol transport in the gut by ABCA1 expression and consequent enhancement of the levels of circulating HDL and their receptor SRB1 in the liver. No hepatic steatosis development was observed in iVP16\u2010LXR\u03b1. In vitro, HDL induced a shift from M1 to M2 phenotype of LPS\u2010stimulated Kupffer cells, decreased TNF\u03b1\u2010induced oxidative stress in hepatocytes and reduced NF\u2010kB activity in both cells. SRB1 silencing reduced TNF\u03b1 gene expression in LPS\u2010stimulated KCs, and NOX\u20101 and IL\u20106 in HepG2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Intestinal activation of LXR\u03b1 modulates hepatic response to injury by increasing circulating HDL levels and SRB1 expression in the liver, thus suggesting this circuit as potential actionable pathway for therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14712","type":"journal-article","created":{"date-parts":[[2020,10,24]],"date-time":"2020-10-24T20:02:00Z","timestamp":1603569720000},"page":"3127-3139","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["HDL cholesterol protects from liver injury in mice with intestinal specific LXR\u03b1 activation"],"prefix":"10.1111","volume":"40","author":[{"given":"Irene","family":"Pierantonelli","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Senigallia Hospital Senigallia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gessica","family":"Lioci","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Marche Polytechnic University Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabio","family":"Gurrado","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Marche Polytechnic University Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora M.","family":"Giordano","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Marche Polytechnic University Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Rychlicki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Marche Polytechnic University Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Bocca","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciano","family":"Trozzi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Marche Polytechnic University Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erica","family":"Novo","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Panera","sequence":"additional","affiliation":[{"name":"Research Area for Multifactorial Diseases, Molecular Genetics of Complex Phenotypes Research Unit Bambino Ges\u00f9 Hospital IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiano","family":"De Stefanis","sequence":"additional","affiliation":[{"name":"Research Area for Multifactorial Diseases, Molecular Genetics of Complex Phenotypes Research Unit Bambino Ges\u00f9 Hospital IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"D\u2019Oria","sequence":"additional","affiliation":[{"name":"Research Area for Multifactorial Diseases, Molecular Genetics of Complex Phenotypes Research Unit Bambino Ges\u00f9 Hospital IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Marzioni","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Marche Polytechnic University Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Maroni","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Marche Polytechnic University Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Parola","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biological Sciences University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7241-6329","authenticated-orcid":false,"given":"Anna","family":"Alisi","sequence":"additional","affiliation":[{"name":"Research Area for Multifactorial Diseases, Molecular Genetics of Complex Phenotypes Research Unit Bambino Ges\u00f9 Hospital IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4399-3359","authenticated-orcid":false,"given":"Gianluca","family":"Svegliati\u2010Baroni","sequence":"additional","affiliation":[{"name":"Obesity Center Marche Polytechnic University Ancona Italy"},{"name":"Liver Injury and Transplant Unit Marche Polytechnic University Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-306842"},{"key":"e_1_2_11_3_1","first-page":"1999","article-title":"Mortality due to cirrhosis and liver cancer in the United States, 1999\u20102016: observational study","volume":"362","author":"Tapper EB","year":"2018","journal-title":"BMJ"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27332"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.11.014"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)33041-7"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.1.266"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.191197"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27883"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12702"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2017.07.010"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000146094.59640.13"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2784"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21875"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22582"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.01.026"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.14-254656"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27352"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2010.07.002"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.142687"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.05.030"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2010.213"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0030-1255353"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2013.03.033"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23804"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI88881"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24711"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230538"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1663"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40139-015-0093-z"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12034"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep20646"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24281"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-001-0476-9"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2008.12.004"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-021317-121550"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2012.10.004"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00280"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14712","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/liv.14712","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.14712","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T01:56:23Z","timestamp":1693878983000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.14712"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,6]]},"references-count":37,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1111\/liv.14712"],"URL":"https:\/\/doi.org\/10.1111\/liv.14712","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,6]]},"assertion":[{"value":"2020-04-05","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-10-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-11-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}