Exendin-4 antagonizes the metabolic action of acylated ghrelinergic signaling in the hypothalamic paraventricular nucleus
| Autor: | David P. Dunn, Erin Howell, Paul J. Currie, Joshua M.R. Bastacky, Shayan Abtahi, Jack T. Salvucci |
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| Rok vydání: | 2019 |
| Předmět: |
Male
endocrine system medicine.medical_specialty 030209 endocrinology & metabolism Biology Carbohydrate metabolism Article Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine medicine Animals Acyl ghrelin Microinjection Respiratory exchange ratio 030304 developmental biology 0303 health sciences digestive oral and skin physiology Neuropeptide Y receptor Ghrelin Rats medicine.anatomical_structure Hypothalamus Exenatide Animal Science and Zoology Nucleus hormones hormone substitutes and hormone antagonists Paraventricular Hypothalamic Nucleus Signal Transduction |
| Zdroj: | General and Comparative Endocrinology. 270:75-81 |
| ISSN: | 0016-6480 |
| DOI: | 10.1016/j.ygcen.2018.10.008 |
| Popis: | In the current study we investigated the interaction of hypothalamic paraventricular nucleus (PVN) glucagon-like peptide-1 (GLP-1) and ghrelin signaling in the control of metabolic function. We first demonstrated that acylated ghrelin injected directly into the PVN reliably altered the respiratory exchange ratio (RER) of adult male Sprague Dawley rats. All testing was carried out during the initial 2 h of the nocturnal cycle using an indirect open circuit calorimeter. Results indicated that acylated ghrelin induced a robust increase in RER representing a shift toward enhanced carbohydrate oxidation and reduced lipid utilization. In contrast, treatment with comparable dosing of des-acyl ghrelin failed to significantly impact metabolic activity. In separate groups of rats we subsequently investigated the ability of exendin-4 (Ex-4), a GLP-1 analogue, to alter acylated ghrelin’s metabolic effects. Rodents were treated with either systemic or direct PVN Ex-4 followed by acyl ghrelin microinjection. While our results showed that both systemic and PVN administration of Ex-4 significantly reduced RER, importantly, Ex-4 pretreatment itself reliably inhibited the impact of ghrelin on RER. Overall, these findings provide increasingly compelling evidence that GLP-1 and ghrelin signaling interact in the neural control of metabolic function within the PVN. |
| Databáze: | OpenAIRE |
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