Objectives: 

Ghrelin is a peptide hormone secreted by the stomach with orexigenic properties that induce food intake trough the activation of hypothalamic AMP activated kinase (AMPK). In rodents fed on normal diet the central administration of ghrelin induces an increase in food intake, however, when fed a high fat diet (HFD) rodents are resistant to the orexigenic effect of ghrelin. Recent data show that Cidea interacts with AMPK Beta-subunit and promotes AMPK degradation trough ubiquitin-dependent pathway. The main goal of this work was to study the mechanism mediating ghrelin resistance in the hypothalamus under HFD.

Materials: 

For this purpose male Sprague-Dawley rats were fed either a low fat diet (LFD) or a HFD. These animals were ICV injected with ghrelin (5ug/ul) or saline. The hypothalamic levels of different proteins were analyzed by western blot using specific antibodies.

Results: 

Food intake induction by ghrelin administration was blunted in rats fed on HFD when compared with rats fed on LFD, which indicated resistance to ghrelin effect caused by HFD. In rats fed on LFD, ghrelin injection induced an increase in hypothalamic levels of phosphorilated forms of AMPK (pAMPK) and its downstream target acetyl-CoA carboxylase (pACC). However in rats fed under HFD, ghrelin treatment caused no changes in pAMPK and pACC levels. Of note, these animals showed a decrease in AMPK beta 1 and AMPK beta 2 levels, which was associated with the increase of the hypothalamic levels of Cidea.

Conclusions: 

These results may suggest that the mechanism of ghrelin resistance could be associated with dysregulation of Cidea and consequently of AMPK in the hypothalamus.