{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T06:40:28Z","timestamp":1790750428462,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T00:00:00Z","timestamp":1660780800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K07940"],"award-info":[{"award-number":["18K07940"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2022,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Hepatic stellate cells (HSCs), the main source of extracellular matrix in hepatic fibrogenesis, produce various cytokines, growth factors, and morphogenetic proteins. Among these, several factors are known to promote hepatocyte lipid accumulation, suggesting that HSCs can be efficient therapeutic targets for non\u2010alcoholic steatohepatitis (NASH). This study aimed to investigate the effects of HSC depletion on the development of hepatic steatosis and fibrosis in a murine NASH model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>C57BL\/6 mice were treated with gliotoxin (GTX), an apoptosis inducer of activated HSCs under the feeding of a choline\u2010deficient <jats:sc>l<\/jats:sc>\u2010amino acid\u2010defined high\u2010fat diet for 4\u00a0weeks. For <jats:italic>in vitro<\/jats:italic> study, Hc3716 cells, immortalized human hepatocytes, were treated with fatty acids in the presence or absence of LX2, immortalized HSCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Choline\u2010deficient <jats:sc>l<\/jats:sc>\u2010amino acid\u2010defined high\u2010fat diet increased pronounced hepatic steatosis, which was attenuated by GTX treatment, together with a reduction in the number of activated HSCs. This change was associated with the downregulation of the peroxisome proliferator\u2010activated receptor gamma (PPAR\u03b3) and its downstream genes, including adipocyte protein 2, cluster of differentiation 36 (CD36), and fatty acid transport protein 1, all of which increase the fatty acid uptake into hepatocytes. As expected, GTX treatment improved hepatic fibrosis. Co\u2010culture of hepatocytes with HSCs enhanced intracellular lipid accumulation, together with the upregulation of PPAR\u03b3 and CD36 protein expressions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In addition to the improvement in hepatic fibrogenesis, depletion of HSCs had a favorable effect on hepatic lipid metabolism in a mouse NASH model, suggesting that HSCs are potentially efficient targets for the treatment of NASH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.15974","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T05:03:42Z","timestamp":1659848622000},"page":"1946-1954","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Depletion of hepatic stellate cells inhibits hepatic steatosis in mice"],"prefix":"10.1111","volume":"37","author":[{"given":"Akihiro","family":"Kawahara","sequence":"first","affiliation":[{"name":"Department of General 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