{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:54:28Z","timestamp":1793642068240,"version":"4.5.1"},"reference-count":44,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2012,4,15]]},"abstract":"<jats:p>These preclinical studies aimed to 1) increase our understanding the dietary induction of nonalcoholic steatohepatitis (NASH), and, 2) further explore the utility and mechanisms of glucagon-like peptide-1 receptor (GLP-1R) agonism in NASH. We compared the effects of a high trans-fat (HTF) or high lard fat (HLF) diet on key facets of nonalcoholic fatty liver disease (NAFLD)\/NASH in Lep<jats:sup>ob<\/jats:sup>\/Lep<jats:sup>ob<\/jats:sup>and C57BL6J (B6) mice. Although HLF-fed mice experienced overall greater gains in weight and adiposity, the addition of trans-fat better mirrored pathophysiological features of NASH (e.g., hepatomegaly, hepatic lipid, and fibrosis). Administration of AC3174, an exenatide analog, and GLP-1R agonist to Lep<jats:sup>ob<\/jats:sup>\/Lep<jats:sup>ob<\/jats:sup>and B6 ameliorated hepatic endpoints in both dietary models. Next, we assessed whether AC3174-mediated improvements in diet-induced NASH were solely due to weight loss in HTF-fed mice. AC3174-treatment significantly reduced body weight (8.3%), liver mass (14.2%), liver lipid (12.9%), plasma alanine aminotransferase, and triglycerides, whereas a calorie-restricted, weight-matched group demonstrated only modest nonsignificant reductions in liver mass (9%) and liver lipid (5.1%) relative to controls. Treatment of GLP-1R-deficient (GLP-1RKO) mice with AC3174 had no effect on body weight, adiposity, liver or plasma indices pointing to the GLP-1R-dependence of AC3174's effects. Interestingly, the role of endogenous GLP-1Rs in NASH merits further exploration as the GLP-1RKO model was protected from the deleterious hepatic effects of HTF. Our pharmacological data further support the clinical evaluation of the utility of GLP-1R agonists for treatment of NASH.<\/jats:p>","DOI":"10.1152\/ajpgi.00476.2011","type":"journal-article","created":{"date-parts":[[2012,1,21]],"date-time":"2012-01-21T02:04:47Z","timestamp":1327111487000},"page":"G762-G772","source":"Crossref","is-referenced-by-count":247,"title":["Glucagon-like peptide-1 receptor agonism improves metabolic, biochemical, and histopathological indices of nonalcoholic steatohepatitis in mice"],"prefix":"10.1152","volume":"302","author":[{"given":"James L.","family":"Trevaskis","sequence":"first","affiliation":[{"name":"Amylin Pharmaceuticals, Inc. San Diego, California;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Amylin Pharmaceuticals, Inc. 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