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Date of Award
Donald V. Coscina
The corticotropin releasing factor (CRF) system is involved in the regulation of feeding and metabolism. Central administration of Ucn 1, a non selective CRF-R agonist, has been shown to produce immediate short-term feeding suppression and lowered respiratory quotients (RQs) in rats. The latter indicates a shift toward preferential oxidation of fatty acids. Centrally administered Ucn 2, a selective CRF-R2 agonist, produced delayed onset feeding suppression. The present study tested the effect of intracerebroventricular administration of Ucn 2, a CRF-R1 antagonist, and a CRF-R2 antagonist on RQ, energy expenditure (EE) and post-test food intake. These variables were also measured after animals were pre-treated with either a CRF-R1 or CRF-R2 antagonist prior to injection of Ucn 2.
Ucn 2 suppressed RQs, which indicated a greater shift toward fat metabolism than would otherwise occur under normal fasting conditions. Ucn 2 did not reliably alter EE or post-metabolic test food intake. Astressin 2-B, a CRF-R2 antagonist did not reliably alter RQ, EE or post-test food intake. The low 300 pmol dose of R121919, a CRF-R1 antagonist, did suppress RQ but had no effect on EE or post-test food intake. The higher doses of R121919 did not alter RQ, EE or post-test food intake. Pre-treatment with either antagonist blocked the effect of Ucn 2 to suppress RQ. These results, taken along with previous research showing Ucn 2 suppresses food intake, suggests that this peptide has the potential to be used as a pharmacological treatment for obesity.
Laplante, Kimberly Anne, "Urocortin 2, A Corticotropin Releasing Factor Receptor 2 Agonist, Alters Energy Substrate Utilization" (2010). Wayne State University Theses. Paper 49.