{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:20:10Z","timestamp":1791188410809,"version":"4.1.0"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":822,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>Activation of hepatic stellate cells (HSCs) is crucial to the development of fibrosis in nonalcoholic fatty liver disease. Quiescent HSCs contain lipid droplets (LDs), whose depletion upon activation induces a fibrogenic gene program. Here we show that liver fatty acid-binding protein (L-Fabp), an abundant cytosolic protein that modulates fatty acid (FA) metabolism in enterocytes and hepatocytes, also modulates HSC FA utilization and in turn regulates the fibrogenic program. L-Fabp expression decreased 10-fold following HSC activation, concomitant with depletion of LDs. Primary HSCs isolated from<\/jats:bold>\n                                 <jats:bold>\n                                    L-FABP\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mice contain fewer LDs than wild-type (WT) HSCs, and exhibit up-regulated expression of genes involved in HSC activation. Adenoviral L-Fabp transduction inhibited activation of passaged WT HSCs and increased both the expression of prolipogenic genes and also augmented intracellular lipid accumulation, including triglyceride and FA, predominantly palmitate. Freshly isolated HSCs from<\/jats:bold>\n                                 <jats:bold>\n                                    L-FABP\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mice correspondingly exhibited decreased palmitate in the free FA pool. To investigate whether<\/jats:bold>\n                                 <jats:bold>\n                                    L-FABP\n                                 <\/jats:bold>\n                                 <jats:bold>deletion promotes HSC activation<\/jats:bold>\n                                 <jats:bold>\n                                    in vivo\n                                 <\/jats:bold>\n                                 <jats:bold>, we fed<\/jats:bold>\n                                 <jats:bold>\n                                    L-FABP\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 and WT mice a high-fat diet supplemented with trans-fatty acids and fructose (TFF). TFF-fed<\/jats:bold>\n                                 <jats:bold>\n                                    L-FABP\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mice exhibited reduced hepatic steatosis along with decreased LD abundance and size compared to WT mice. In addition, TFF-fed<\/jats:bold>\n                                 <jats:bold>\n                                    L-FABP\n                                 <\/jats:bold>\n                                 <jats:bold>\n                                    \u2212\/\u2212 mice exhibited decreased hepatic fibrosis, with reduced expression of fibrogenic genes, compared to WT mice.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion\n                                 <\/jats:bold>\n                                 <jats:bold>:<\/jats:bold>\n                                 <jats:bold>\n                                    L-FABP\n                                 <\/jats:bold>\n                                 <jats:bold>deletion attenuates both diet-induced hepatic steatosis and fibrogenesis, despite the observation that L-Fabp paradoxically promotes FA and LD accumulation and inhibits HSC activation<\/jats:bold>\n                                 <jats:bold>\n                                    in vitro\n                                 <\/jats:bold>\n                                 <jats:bold>. These findings highlight the importance of cell-specific modulation of hepatic lipid metabolism in promoting fibrogenesis in nonalcoholic fatty liver disease.<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.26318","type":"journal-article","created":{"date-parts":[[2013,2,11]],"date-time":"2013-02-11T09:58:42Z","timestamp":1360576722000},"page":"2202-2212","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":80,"title":["Liver fatty acid binding protein (L-Fabp) modulates murine stellate cell activation and diet-induced nonalcoholic fatty liver disease"],"prefix":"10.1097","volume":"57","author":[{"given":"Anping","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youcai","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fong-Fu","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Kennedy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haowei","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Turk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Brunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth P.","family":"Newberry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas O.","family":"Davidson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-16-20241201","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1053\/j.gastro.2012.04.001","article-title":"The diagnosis and management of nonalcoholic fatty liver disease: practice guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology.","volume":"142","author":"Chalasani","year":"2012","journal-title":"Gastroenterology"},{"key":"R2-16-20241201","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1126\/science.1204265","article-title":"Human fatty liver disease: old questions and new insights.","volume":"332","author":"Cohen","year":"2011","journal-title":"Science"},{"key":"R3-16-20241201","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1146\/annurev-biochem-061009-102430","article-title":"Lipid droplets and cellular lipid metabolism.","volume":"81","author":"Walther","year":"2012","journal-title":"Annu Rev Biochem"},{"key":"R4-16-20241201","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1194\/jlr.R700014-JLR200","article-title":"Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis.","volume":"48","author":"Brasaemle","year":"2007","journal-title":"J Lipid Res"},{"key":"R5-16-20241201","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1007\/s13105-011-0110-6","article-title":"Role of lipid droplet proteins in liver steatosis.","volume":"67","author":"Okumura","year":"2011","journal-title":"J Physiol Biochem"},{"key":"R6-16-20241201","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.1002\/hep.1840070609","article-title":"Biochemical characteristics of isolated rat liver stellate cells.","volume":"7","author":"Yamada","year":"1987","journal-title":"Hepatology"},{"key":"R7-16-20241201","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/BF02533990","article-title":"Liver parenchymal cells differ from the fatstoring cells in their lipid 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