{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:27:33Z","timestamp":1793147253824,"version":"4.5.0"},"reference-count":29,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T00:00:00Z","timestamp":1706486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22K17845"],"award-info":[{"award-number":["JP22K17845"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K21273"],"award-info":[{"award-number":["JP21K21273"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Nonalcoholic steatohepatitis (NASH) occurs worldwide and is characterized by lipid accumulation in hepatocytes, hepatic inflammation, fibrosis, and an increased risk of cirrhosis. Although a major proportion of NASH patients exhibit obesity and insulin resistance, 20% lack a high body mass and are categorized as \u201cnon-obese NASH\u201d. Time-restricted feeding (TRF), limiting daily food intake within certain hours, improves obesity, lipid metabolism, and liver inflammation. Here, we determined whether TRF affects NASH pathology induced by a choline-deficient high-fat diet (CDAHFD), which does not involve obesity. TRF ameliorated the increase in epididymal white adipose tissue and plasma alanine transaminase and aspartate transaminase levels after 8 weeks of a CDAHFD. Although gene expression of <jats:italic>TNF alpha<\/jats:italic> in the liver was suppressed by TRF, it did not exhibit a suppressive effect on hepatic lipid accumulation, gene expression of cytokines and macrophage markers (<jats:italic>Mcp1<\/jats:italic>, <jats:italic>IL1b<\/jats:italic>, <jats:italic>F4\/80<\/jats:italic>), or fibrosis, as evaluated by Sirius red staining and western blot analysis of alpha-smooth muscle actin. A CDAHFD-induced increase in gene expression related to fibrogenesis (<jats:italic>Collagen 1a1<\/jats:italic> and <jats:italic>TGF\u03b2<\/jats:italic>) was neither suppressed by TRF nor that of alpha-smooth muscle actin but was increased by TRF. Our results indicated that TRF has a limited suppressive effect on CDAHFD-induced NASH pathology.<\/jats:p>","DOI":"10.1371\/journal.pone.0296950","type":"journal-article","created":{"date-parts":[[2024,1,29]],"date-time":"2024-01-29T18:27:50Z","timestamp":1706552870000},"page":"e0296950","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Time-restricted feeding has a limited effect on hepatic lipid accumulation, inflammation and fibrosis in a choline-deficient high-fat diet-induced murine NASH model"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9656-2619","authenticated-orcid":true,"given":"Tomoyuki","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutaka","family":"Oishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,1,29]]},"reference":[{"issue":"1","key":"pone.0296950.ref001","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"ZM Younossi","year":"2016","journal-title":"Hepatology"},{"issue":"1","key":"pone.0296950.ref002","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1002\/hep.29367","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: 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Friedman","year":"2018","journal-title":"Nat Med"},{"issue":"3","key":"pone.0296950.ref006","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/j.jcmgh.2021.05.010","article-title":"Nonalcoholic Steatohepatitis and HCC in a Hyperphagic Mouse Accelerated by Western Diet","volume":"12","author":"S Ganguly","year":"2021","journal-title":"Cell Mol Gastroenterol Hepatol"},{"issue":"5","key":"pone.0296950.ref007","doi-asserted-by":"crossref","first-page":"2454","DOI":"10.1016\/j.ajpath.2011.07.014","article-title":"Melanocortin 4 receptor-deficient mice as a novel mouse model of nonalcoholic steatohepatitis","volume":"179","author":"M Itoh","year":"2011","journal-title":"Am J Pathol"},{"issue":"11","key":"pone.0296950.ref008","doi-asserted-by":"crossref","first-page":"1707","DOI":"10.1016\/j.drudis.2017.06.007","article-title":"Mouse models of nonalcoholic steatohepatitis in preclinical drug development","volume":"22","author":"HH Hansen","year":"2017","journal-title":"Drug 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