Dexamethasone-induced hepatic lipogenesis is insulin dependent in chickens (Gallus gallus domesticus)

Abstract

Hepatic lipogenesis-induced de novo by glucocorticoids (GCs) is associated with the development of obesity and diabetes mellitus. The interaction of GCs and insulin in the regulation of hepatic lipogenesis remains unclear. The effect of exogenous GC administration on hepatic lipogenesis and fat deposition was studied in broiler chickens (Gallus gallus domesticus), and the role of insulin in the effect of GCs on hepatic lipogenesis was evaluated. Dexamethasone (DEX, 2 mg/kg body mass (BM)) administration for 3-d resulted in BM loss and increased liver and cervical adipose tissue mass compared to control and pair-fed counterparts. DEX treatment significantly (P < 0.05) increased plasma level of insulin in either the fed or fasting state, whereas plasma glucose level was only increased in the fed state. In fasted chickens, DEX treatment significantly (P < 0.01) upregulated the hepatic mRNA levels of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). In the fed state, the mRNA levels of ACC and FAS were not significantly influenced by DEX treatment, nor was FAS activity. In cultured primary hepatocytes, combined DEX and insulin significantly upregulated the transcription of the genes for FAS (1.34-fold) and malic enzyme (1.72-fold). By contrast, the expression of sterol response element-binding protein-1 (SREBP-1) was significantly upregulated by insulin (1.67-fold) regardless of DEX. In abdominal adipose tissue, DEX treatment had no significant (P>0.05) effect on the activities and transcription of FAS. The expressions of lipoprotein lipase and peroxisome proliferator-activated receptor-γ were not significantly (P>0.05) affected by DEX treatment in either the fasting or fed state. The results indicate that DEX increased hepatic de novo lipogenesis via the increased activity and expression of lipogenic enzymes. Insulin-activated gene expression for SREBP-1 is suggested to be involved in stress-augmented hepatic lipogenesis.