Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 302, Issue 8, Pages G850-G863Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00378.2011
Keywords
insulin resistance; steatosis; visceral obesity
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Funding
- Natural Science and Engineering Research Council of Canada
- Canadian Diabetes Association
- Ontario Graduate Scholarship
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Consumption of a high-fat diet rapidly exacerbates the development of fatty liver disease that occurs with chronically elevated glucocorticoids. Am J Physiol Gastrointest Liver Physiol 302: G850-G863, 2012. First published January 19, 2012; doi:10.1152/ajpgi.00378.2011.-Chronically elevated glucocorticoids (GCs) and a high-fat diet (HFD) independently induce insulin resistance, abdominal obesity, and nonalcoholic fatty liver disease (NAFLD). GCs have been linked to increased food intake, particularly energy-dense comfort foods. Thus we examined the synergistic actions of GCs and HFD on hepatic disease development in a new rodent model of chronically elevated GCs. 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 = 8-10 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.
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