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Six-week-old male Sprague-Dawley rats received exogenous GCs, via subcutaneous implantation of four 100-mg corticosterone (Cort) pellets, to elevate basal GC levels for 16 days ( n = 8\u201310 per group). Another subset of animals received wax pellets (placebo) to serve as controls. Animals from each group were randomly assigned to receive a 60% HFD or a standard high-carbohydrate (13% fat and 60% carbohydrate) diet. Cort + HFD resulted in central obesity, despite a relative weight loss, a 4-fold increase in hepatic lipid content, hepatic fibrosis, and a 2.8-fold increase in plasma alanine aminotransferase levels compared with placebo + chow controls. Hepatic injury developed independent of inflammation, as plasma haptoglobin levels were reduced with Cort treatment. Insulin resistance and hepatic steatosis occurred with Cort alone; these outcomes were further exacerbated by the HFD in the presence of elevated Cort. In addition to fatty liver, the Cort + HFD group also developed severe insulin resistance, hyperinsulinemia, hyperglycemia, and hypertriglyceridemia, which were not evident with HFD or Cort alone. Thus a HFD dramatically exacerbates the development of NAFLD and characteristics of the metabolic syndrome in conditions of chronically elevated Cort.<\/jats:p>","DOI":"10.1152\/ajpgi.00378.2011","type":"journal-article","created":{"date-parts":[[2012,1,21]],"date-time":"2012-01-21T02:04:47Z","timestamp":1327111487000},"page":"G850-G863","source":"Crossref","is-referenced-by-count":75,"title":["Consumption of a high-fat diet rapidly exacerbates the development of fatty liver disease that occurs with chronically elevated glucocorticoids"],"prefix":"10.1152","volume":"302","author":[{"given":"Anna M.","family":"D'souza","sequence":"first","affiliation":[{"name":"Muscle Health Research Center and Physical Activity and Chronic Disease Unit, School of Kinesiology and Health Science, Faculty of Health, York University,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline L.","family":"Beaudry","sequence":"additional","affiliation":[{"name":"Muscle Health Research 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