Consumption of a high-fat diet rapidly exacerbates the development of fatty liver disease that occurs with chronically elevated glucocorticoids.

Abstract

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.

• Authors: Anna M D'souza, Jacqueline L Beaudry, Andrei A Szigiato, Stephen J Trumble, Laelie A Snook, Arend Bonen, Adria Giacca, Michael C Riddell
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 302 Issue 8 Pg. G850-63 (Apr 15 2012) ISSN: 1522-1547 [Electronic] United States
• PMID: 22268100 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CD36 Antigens
• Ceramides
• Fatty Acids, Nonesterified
• Glucocorticoids
• Protein Kinase C-delta
• Protein Kinase C-epsilon
• Corticosterone

Topics

• Adipose Tissue (pathology)
• Adrenal Glands (pathology)
• Animals
• Atrophy
• Blotting, Western
• Body Weight (physiology)
• CD36 Antigens (metabolism)
• Cell Membrane (enzymology)
• Ceramides (metabolism)
• Circadian Rhythm (drug effects)
• Corticosterone (blood, pharmacology)
• Cytosol (enzymology)
• Diet, High-Fat (adverse effects)
• Fatty Acids, Nonesterified (blood)
• Fatty Liver (chemically induced, pathology)
• Glucocorticoids (metabolism, pharmacology)
• Insulin Resistance
• Lipid Metabolism (drug effects)
• Liver (metabolism, pathology)
• Liver Cirrhosis (pathology)
• Male
• Muscle, Skeletal (pathology)
• Portal Vein (metabolism)
• Protein Kinase C-delta (metabolism)
• Protein Kinase C-epsilon (metabolism)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction