{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T19:33:01Z","timestamp":1784403181733,"version":"3.55.0"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T00:00:00Z","timestamp":1559779200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2019,8]]},"abstract":"<jats:p>Lipoprotein lipase (LPL) plays a central role in incorporating plasma lipids into tissues and regulates lipid metabolism and energy balance in the human body. Conversely, LPL expression is almost absent in normal adult livers. Therefore, its physiological role in the liver remains unknown. We aimed to elucidate the role of LPL in the pathophysiology of nonalcoholic steatohepatitis (NASH), a hepatic manifestation of obesity. Hepatic stellate cell (HSC)\u2013specific LPL\u2010knockout (<jats:italic toggle=\"yes\">LplHSC\u2010KO\n                           <\/jats:italic>) mice, LPL\u2010floxed (<jats:italic toggle=\"yes\">Lplfl\/fl\n                           <\/jats:italic>) mice, or double\u2010mutant toll\u2010like receptor 4\u2013deficient (<jats:italic toggle=\"yes\">Tlr4\u2212\/\u2212\n                           <\/jats:italic>) <jats:italic toggle=\"yes\">LplHSC\u2010KO\n                           <\/jats:italic> mice were fed a high\u2010fat\/high\u2010cholesterol diet for 4 weeks to establish the nonalcoholic fatty liver model or an high\u2010fat\/high\u2010cholesterol diet for 24 weeks to establish the NASH model. Human samples, derived from patients with nonalcoholic fatty liver disease, were also examined. In human and mouse NASH livers, serum obesity\u2010related factors, such as free fatty acid, leptin, and interleukin\u20106, dramatically increased the expression of LPL, specifically in HSCs through signal transducer and activator of transcription 3 signaling, as opposed to that in hepatocytes or hepatic macrophages. In the NASH mouse model, liver fibrosis was significantly reduced in <jats:italic toggle=\"yes\">LplHSC\u2010KO\n                           <\/jats:italic> mice compared with that in <jats:italic toggle=\"yes\">Lplfl\/fl\n                           <\/jats:italic> mice. Nonenzymatic LPL\u2010mediated cholesterol uptake from serum lipoproteins enhanced the accumulation of free cholesterol in HSCs, which amplified TLR4 signaling, resulting in the activation of HSCs and progression of hepatic fibrosis in NASH. <jats:italic toggle=\"yes\">Conclusion<\/jats:italic>: The present study reveals the pathophysiological role of LPL in the liver, and furthermore, clarifies the pathophysiology in which obesity, as a background factor, exacerbates NASH. The LPL\u2010mediated HSC activation pathway could be a promising therapeutic target for treating liver fibrosis in NASH.<\/jats:p>","DOI":"10.1002\/hep4.1383","type":"journal-article","created":{"date-parts":[[2019,6,6]],"date-time":"2019-06-06T12:26:07Z","timestamp":1559823967000},"page":"1098-1112","source":"Crossref","is-referenced-by-count":54,"title":["Lipoprotein Lipase Up\u2010regulation in Hepatic Stellate Cells Exacerbates Liver Fibrosis in Nonalcoholic Steatohepatitis in Mice"],"prefix":"10.1097","volume":"3","author":[{"given":"Toshiaki","family":"Teratani","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine,Keio University School of Medicine,Shinjuku\u2010ku,Tokyo,Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kengo","family":"Tomita","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Internal Medicine,National Defense Medical 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