Year: 2002
Type: article
Abstract: Central administration of glucagon-like peptide-1 (GLP-1) has been proposed to contribute to the regulation of food intake, as it causes anorexia in the rodent.However, GLP-1 also causes symptoms of visceral illness.Whether GLP-1-induced anorexia is due to a role in energy balance or if it is secondary to visceral illness is a matter of debate.These studies demonstrate that GLP-1 is involved in both the regulation of food intake and mediating the response to visceral illness.When injected into the fourth ventricle, GLP-1 reduces food intake with no concomitant conditioned taste aversion (CTA).This is in contrast to the effects of GLP-1 injected directly into the central nucleus of the amygdala.In this case, there is no reduction in food intake, however rats developed a CTA.These results indicate that GLP-1 a flexible system that can be activated under different circumstances to alter the ingestion of nutrients and/or produce other visceral illness responses depending on the ascending pathways of the GLP-1 system that are recruited.Recent data also imply the involvement of GLP-1 with the hypothalamicpituitary-adrenal (HPA) axis.Administration of interoceptive stressors such as lithium chloride (LiCl) increases neuronal activity in GLP-1-containing neurons, and administration of GLP-1 increases neuronal activity in the hypothalamic paraventricular nucleus (PVN).We therefore hypothesized that GLP-1 mediates the HPA response to interoceptive stressors.We further hypothesized that the GLP-1 system would not be involved in the response to psychogenic stressors, as GLP-1-producing neurons originate in the hindbrain and the processing of psychogenic stressors is largely independent of hindbrain activity.We show that central GLP-1 increases levels of the stress-activated IV hormones ACTH and corticosterone, and increases levels of anxiety as measured by the elevated plus maze.The endocrine response is preferentially activated by GLP-1 administration in the PVN while the anxiety response is preferentially activated by administration in the CeA.Furthermore, GLP-1 antagonists block increases in stress hormones associated with the toxin LiCl and both the endocrine and anxiety responses to vertical heights.Therefore, the current data implicate a role for the GLP-1 system as a critical mediator of multiple stress responses.V VI ACKNOWLEDGEMENTS I would like to thank my advisor, Randy J. Seeley, for providing the support to pursue projects that were both interesting and challenging.Additionally, I am eternally grateful for your support throughout my relatively unconventional graduate school life.I would also like to thank Stephen C. Woods, who first gave me the chance to get started in this field.Your support over the years has been so important to me.You and Randy have made it possible for me to realize many of
Author: Kimberly P. Kinzig
Institution: University of Cincinnati
Language: English
Subfield: Endocrine and Autonomic Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2462696729