Glucocorticoids induced high fat diet preference via activating hypothalamic AMPK signaling in chicks

- GCs could evoke a particular appetite for foods rich in fat or energy.
- Hypothalamic CRH and NPY gene at least partially accounts for the GC-induced food preference for HFD.
- Hypothalamic AMPK is involved in the regulation of GC-induced changes in food consumption.

Glucocorticoids (GCs) stimulate appetite, contributing to enhanced fat deposition. Our present study was conducted to determine whether GCs could evoke an appetite specifically for fat-rich diets in chicks. Chicks were subjected to a subcutaneous injection of corticosterone (CORT, 2 mg/kg body weight/day) or corn oil (control), and food preference was tested. The results showed that CORT-chicks consumed more high-fat diet (HFD) compared with controls. In HFD-fed chicks, hypothalamic phosphorylated AMP-activated protein kinase α (AMPKα) and neuropeptide Y (NPY) mRNA levels were increased by CORT treatment. Activating AMPK with 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside, an AMPK activator, via intracerebroventricular injection further enhanced the CORT-induced HFD consumption and concurrently up-regulated NPY mRNA levels and phosphorylated AMPKα and acetyl-coenzyme A carboxylase levels. The dramatic increase in HFD consumption and upregulation of NPY mRNA levels and phospho-AMPKα levels induced by peripheral CORT injection was not altered by intracerebroventricular infusion of compound C (4-16 μg), an AMPK inhibitor. In conclusion, CORT challenge caused a HFD preference by enhancing the AMPK pathway in the hypothalamus.