内科学
内分泌学
胰岛素抵抗
非酒精性脂肪肝
脂肪肝
高胰岛素血症
脂肪变性
皮质酮
医学
高甘油三酯血症
胰岛素
生物
甘油三酯
胆固醇
激素
疾病
作者
Anna M. D'souza,Jacqueline L. Beaudry,Andrei-Alexandru Szigiato,Stephen J. Trumble,Laelie A. Snook,Arend Bonen,Adria Giacca,Michael C. Riddell
出处
期刊:American Journal of Physiology-gastrointestinal and Liver Physiology
[American Physiological Society]
日期:2012-04-15
卷期号:302 (8): G850-G863
被引量:75
标识
DOI:10.1152/ajpgi.00378.2011
摘要
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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