{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T17:50:18Z","timestamp":1790445018448,"version":"4.1.0"},"reference-count":122,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK112360"],"award-info":[{"award-number":["DK112360"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nonalcoholic fatty liver disease (NAFLD) is a global health problem. Identification of factors contributing to the onset and progression of NAFLD have the potential to direct novel strategies to combat NAFLD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We examined the time course of western diet (WD)-induced NAFLD and its progression to nonalcoholic steatohepatitis (NASH) in age-matched female and male\n                      <jats:italic>Ldlr<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>-\/-<\/jats:italic>\n                      <\/jats:sup>\n                      mice, with time-points at 1, 4, 8, 20 and 40 weeks on the WD. Controls included\n                      <jats:italic>Ldlr<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>-\/-<\/jats:italic>\n                      <\/jats:sup>\n                      mice maintained on a purified low-fat diet (LFD) for 1 and 40 weeks. The approach included quantitation of anthropometric, plasma and liver markers of disease, plus hepatic histology, lipids, oxylipins, gene expression and selected metabolites.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      One week of feeding the WD caused a significant reduction in hepatic essential fatty acids (EFAs: 18:2, \u03c96, 18:3, \u03c93) which preceded the decline in many C\n                      <jats:sub>20-22<\/jats:sub>\n                      \u03c93 and \u03c96 polyunsaturated fatty acids (PUFA) and PUFA-derived oxylipins after 4 weeks on the WD. In addition, expression of hepatic inflammation markers (\n                      <jats:italic>CD40<\/jats:italic>\n                      ,\n                      <jats:italic>CD44<\/jats:italic>\n                      ,\n                      <jats:italic>Mcp1<\/jats:italic>\n                      ,\n                      <jats:italic>Nlrp3<\/jats:italic>\n                      ,\n                      <jats:italic>TLR2<\/jats:italic>\n                      ,\n                      <jats:italic>TLR4<\/jats:italic>\n                      ,\n                      <jats:italic>Trem2<\/jats:italic>\n                      ) increased significantly in both female &amp; male mice after one week on the WD. These markers continued to increase over the 40-week WD feeding study. WD effects on hepatic EFA and inflammation preceded all significant WD-induced changes in body weight, insulin resistance (HOMA-IR), oxidative stress status (GSH\/GSSG ratio) and histological and gene expression markers of macrosteatosis, extracellular matrix remodeling and fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Our findings establish that feeding\n                      <jats:italic>Ldlr<\/jats:italic>\n                      <jats:sup>\n                        <jats:italic>-\/-<\/jats:italic>\n                      <\/jats:sup>\n                      mice the WD rapidly lowered hepatic EFAs and induced key inflammatory markers linked to NASH. Since EFAs have an established role in inflammation and hepatic inflammation plays a major role in NASH, we suggest that early clinical assessment of EFA status and correcting EFA deficiencies may be useful in reducing NASH severity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0292432","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T13:30:45Z","timestamp":1697031045000},"page":"e0292432","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":10,"title":["Time course of western diet (WD) induced nonalcoholic steatohepatitis (NASH) in female and male Ldlr-\/- mice"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7099-1837","authenticated-orcid":true,"given":"Melinda H.","family":"Spooner","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Garcia-Jaramillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. Denise","family":"Apperson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane V.","family":"L\u00f6hr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9473-6283","authenticated-orcid":true,"given":"Donald B.","family":"Jump","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"issue":"2","key":"pone.0292432.ref001","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/MCO.0000000000000539","article-title":"Omega-3 fatty acids and nonalcoholic fatty liver disease in adults and children: where do we stand?","volume":"22","author":"MH Spooner","year":"2019","journal-title":"Curr Opin Clin Nutr Metab 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