{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T08:38:59Z","timestamp":1772008739911,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2011,2,24]],"date-time":"2011-02-24T00:00:00Z","timestamp":1298505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:p><jats:bold>Aim:\u2002<\/jats:bold> Chronic ethanol exposure impairs insulin signaling in the liver. Peroxisome\u2010proliferator activated receptor (PPAR) agonists function as insulin sensitizers and are used to treat type 2 diabetes mellitus. We examined the therapeutic effectiveness of PPAR agonists in reducing alcoholic hepatitis and hepatic insulin resistance in a model of chronic ethanol feeding.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Adult male Long Evans rats were pair fed with isocaloric liquid diets containing 0% (control) or 37% ethanol (caloric content; 9.2% v\/v) for 8\u2003weeks. After 3\u2003weeks on the diets, the rats were treated with vehicle, or a PPAR\u2010\u03b1, PPAR\u2010\u03b4 or PPAR\u2010\u03b3 agonist twice weekly by i.p. injection. Livers were harvested for histopathological, gene expression (reverse transcription polymerase chain reaction), protein (western and ELISA) and receptor binding studies.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> Ethanol\u2010fed rats developed steatohepatitis with disordered hepatic chord architecture, increased hepatocellular apoptosis, reduced binding to the insulin, insulin\u2010like growth factor (IGF)\u20101 and IGF\u20102 receptors, and decreased expression of glyceraldehyde\u20103\u2010phosphate dehydrogenase and aspartyl\u2010(asparaginyl)\u2010\u03b2\u2010hydroxylase (mediating remodeling), which are regulated by insulin\/IGF signaling. PPAR\u2010\u03b1, PPAR\u2010\u03b4 or PPAR\u2010\u03b3 agonist treatments reduced the severity of ethanol\u2010mediated liver injury, including hepatic architectural disarray and steatosis. In addition, PPAR\u2010\u03b4 and PPAR\u2010\u03b3 agonists reduced insulin\/IGF resistance and increased insulin\/IGF\u2010responsive gene expression.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> PPAR agonists may help reduce the severity of chronic ethanol\u2010induced liver injury and insulin\/IGF resistance, even in the context of continued high\u2010level ethanol consumption.<\/jats:p>","DOI":"10.1111\/j.1872-034x.2011.00775.x","type":"journal-article","created":{"date-parts":[[2011,2,26]],"date-time":"2011-02-26T15:32:26Z","timestamp":1298734346000},"page":"386-398","source":"Crossref","is-referenced-by-count":35,"title":["Peroxisome proliferator\u2010activated receptor agonist treatment of alcohol\u2010induced hepatic insulin resistance"],"prefix":"10.1111","volume":"41","author":[{"given":"Suzanne M.","family":"de la 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