{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:40:39Z","timestamp":1790404839762,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,3,13]],"date-time":"2012-03-13T00:00:00Z","timestamp":1331596800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Hepatosteatosis is an essential step in liver disease progression. However, the mechanisms that mediate the progression of hepatosteatosis and the optimal inhibitor of them remain largely unclear. The sympathetic nervous system (<jats:styled-content style=\"fixed-case\">SNS<\/jats:styled-content>) is responsible for the lipid metabolism and the accumulation of collagen that occurs in an injured liver. Medicines that inhibit this pathway may be a relevant treatment for the hepatosteatosis, and then reduce the liver injury that progresses through the stage of steatosis to fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using an ethanol\u2010liquid\u2010diet\u2010fed rat model of alcohol fatty liver disease (<jats:styled-content style=\"fixed-case\">AFLD<\/jats:styled-content>), we studied the effects of carvedilol, which can block the <jats:styled-content style=\"fixed-case\">SNS<\/jats:styled-content> completely via \u03b21, \u03b22, and \u03b11 adrenergic receptors, on the sympathetic tone, hepatosteatosis, and fibrosis based on histological, immunohistochemical, <jats:styled-content style=\"fixed-case\">W<\/jats:styled-content>estern blot, and reverse transcriptase polymerase chain reaction analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Carvedilol inhibited the ethanol\u2010induced whole\u2010body and hepatic sympathetic activities based on the serum 3\u2010methoxy\u20104\u2010hydroxyphenylglycol level and hepatic tyrosine hydroxylase expression. Carvedilol attenuated the hepatosteatosis, as evidenced by reduced hepatic triglyceride level and the accumulation of fatty droplets within hepatocytes, down\u2010regulated fatty acid synthase and sterol regulatory element binding protein\u20101, and up\u2010regulated peroxisome proliferator\u2010activated receptor\u2010\u03b1. No fibrosis signs were shown in our rat model. Carvedilol inhibited ethanol\u2010induced the thickening of zone 3 vessel walls, reduced the activation of hepatic stellate cells (<jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s), and decreased the induction of collagen, transforming growth factor \u03b21, and tissue inhibitor of metalloproteinases\u20101. Tumor necrosis factor \u03b1 (<jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1) was expressed on the activated <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s and inhibited by carvedilol based on the immunohistochemical double staining analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Ethanol metabolism\u2010induced lipogenesis may trigger the <jats:styled-content style=\"fixed-case\">SNS<\/jats:styled-content>\u2010activated <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s feedback loop, and then induct the activated <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s and the activated <jats:styled-content style=\"fixed-case\">HSC<\/jats:styled-content>s\u2013derived <jats:styled-content style=\"fixed-case\">TNF<\/jats:styled-content>\u2010\u03b1, the mediator of lipogenesis, overproduction. Carvedilol may block this feedback loop via antisympathetic activity and demonstrate its preventive role on the development of hepatosteatosis in rat with <jats:styled-content style=\"fixed-case\">AFLD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1530-0277.2012.01773.x","type":"journal-article","created":{"date-parts":[[2012,3,13]],"date-time":"2012-03-13T18:42:55Z","timestamp":1331664175000},"page":"1587-1599","source":"Crossref","is-referenced-by-count":28,"title":["Carvedilol Attenuates the Progression of Alcohol Fatty Liver Disease in Rats"],"prefix":"10.1111","volume":"36","author":[{"given":"Jinyao","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Legal Medicine Yamaguchi University Graduate School of Medicine Ube Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Takase","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine Yamaguchi University Graduate School of Medicine Ube 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