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Comparative studies on ASH and NASH have been hampered by the use of different animal models with confounding variables, particularly those with extreme genetic, toxic, and malnutrition etiologies. The mouse intragastric model circumvents these problems and reproduces the natural course and etiological background of ASH and NASH. Further, our recent work reproduces a profound synergism between the two in the model. Intracellular accumulation of neural lipids is a hallmark biochemical feature of ASH and NASH. Although impaired lipid oxidation and export may contribute to this pathological change, enhanced lipogenic regulation is frequently encountered, as characterized by induction of lipogenic or adipogenic transcription factors (peroxisome proliferator\u2010activated receptor [<jats:italic>PPAR<\/jats:italic>\u03b3], liver X receptor \u03b1[<jats:italic>LXR<\/jats:italic>\u03b1], sterol\u2010regulatory element\u2010binding protein\u20101c [<jats:italic>SREBP<\/jats:italic>\u2010<jats:italic>1c<\/jats:italic>]). In contrast, we have recently defined transdifferentiation of hepatic stellate cells (HSC), a pivotal event in liver fibrogenesis, as an \u2018antilipogenic\u2019 or \u2018anti\u2010adipogenic\u2019 phenomenon. Thus, there is an apparent paradox between hepatocytes and HSC in steatohepatitis in terms of the outcome of lipogenic regulation. Our recent work suggests that defective insulin signaling in activated HSC may be responsible for this paradox. Further, activated Wnt signaling is implicated in \u2018anti\u2010adipogenic\u2019 stellate cell transdifferentiation in liver fibrogenesis.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2007.05294.x","type":"journal-article","created":{"date-parts":[[2008,3,12]],"date-time":"2008-03-12T20:45:39Z","timestamp":1205354739000},"update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Fat paradox of steatohepatitis"],"prefix":"10.1111","volume":"23","author":[{"given":"Hidekazu","family":"Tsukamoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyun","family":"She","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saswati","family":"Hazra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaohong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,3,12]]},"reference":[{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.64.070195.002021"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/130.12.3116S"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.22.7558-7568.2001"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.16.5989-5999.2002"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2001-0210"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.844900"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.850400"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215593"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.9.1096"},{"key":"e_1_2_8_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.111138698"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00872-3"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00516.2001"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1133426100"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118703"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119839"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11245"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0016-5085(03)00276-2"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202411200"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701329200"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21614"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300043200"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200317223"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210062200"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1262-3636(07)70061-7"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI23621"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.36780"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20427"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M006577200"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M410078200"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310284200"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M510094200"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00411.2003"},{"key":"e_1_2_8_34_2","unstructured":"ChengJH SheH HanY\u2010Pet\u2003al.Wnt antagonism inhibits hepatic stellate cell activation and liver fibrosis.Am. 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