| Consumption of a High Fat Diet Rapidly Exacerbates the Development of Fatty Liver Disease that Occurs with Chronically Elevated Glucocorticoids. | |
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MedLine Citation:
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PMID: 22268100 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Chronically elevated glucocorticoids (GCs) and a high fat diet (HFD) independently induce insulin resistance, abdominal obesity and non-alcoholic fatty liver disease (NAFLD). GCs themselves 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 then randomly assigned to receive either a 60% HFD or a standard high carbohydrate diet (13% fat; 60% carbohydrate). CORT and a HFD in combination 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 relative to placebo chow controls. Development of hepatic injury occurred independent of inflammation, as plasma haptoglobin levels were reduced with CORT treatment. Insulin resistance and hepatic steatosis occurred with CORT exposure alone; these outcomes were further exacerbated when HFD was given 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 was not evident with either HFD or CORT treatment 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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Authors:
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Anna M D'souza; Jacqueline L Beaudry; Andrei A Szigiato; Stephen J Trumble; Laelie A Snook; Arend Bonen; Adria Giacca; Michael C Riddell |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-19 |
Journal Detail:
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Title: American journal of physiology. Gastrointestinal and liver physiology Volume: - ISSN: 1522-1547 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901227 Medline TA: Am J Physiol Gastrointest Liver Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1York University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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