Endocrine Abstracts (2011) 26 P190

The role of centrally applied ghrelin on hypothalamic AMPK activity and pituitary-adrenal responses in differently fed rats

Darko Stevanovic1, Verica Milosevic2, Dejan Nesic1, Dragan Micic3, Mirjana Sumarac-Dumanovic3, Vera Popovic3 & Vesna Starcevic1


1Institute of Medical Physiology, School of Medicine, University of Belgrade, Belgrade, Serbia; 2Institute for Biological Research Sinisa Stankovic, University of Belgrade, Belgrade, Serbia; 3Institute of Endocrinology, Diabetes and Diseases of Metabolism, School of Medicine, University of Belgrade, Belgrade, Serbia.


The pandemic increase of obesity, malnutrition and associated comorbidities encouraged intensive studies on energy balance control. Ghrelin is a brain-gut orexigenic hormone that is involved in both the short-term and long-term regulation of energy homeostasis. The aim of this research was to investigate the role of centrally applied ghrelin on the pituitary morphofunctional features and corticosterone secretion in normal-fed, food-restricted and obese 8 weeks old Wistar male rats, as well as to examine changes in their hypothalamic AMP-activated protein kinase (AMPK) activity. After 4 weeks of normal feeding (NF group), progressive food restriction (FR group) and high-fat diet (HF group), rats received 5 daily injections of ghrelin and/or saline i.c.v. Blood samples, hypothalami and pituitaries were excised for further analyses 1 h after the last i.c.v. injection. Results showed that i.c.v. ghrelin had orexigenic effect in all examined groups, and it increased pituitary corticotroph cell volumes and their secretion. Corticosterone blood levels were elevated after central ghrelin treatment in NF and FR groups, while remained unchanged in HF group. Hypothalamic AMPK activity was increased in FR group and decreased in HF group when compared to NF group, and i.c.v. ghrelin treatment increased AMPK phosphorilation in NF and HF groups, while had no effect in FR group. In conclusion, centrally applied ghrelin had significant effect in energy balance regulation, mostly under preserved energy homeostasis and increased hypothalamic AMPK activity in normal-fed and obese rats.

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