Presentation Details
| Using Targeted Recombination in Active Populations (TRAP), 2-Photon Calcium Imaging, and Metabolic Monitoring to Investigate the Effect of Administration of the Glucagon-like Peptide 1 (GLP-1) Agonist Semaglutide in Mice. Debra A Fadool1, 2, 3, Madison A Herrboldt4, Saptarsi Mitra1, 3, Giorgio Belperio1, 3, Dale M Wachowiak4. 1Program in Neuroscience, Florida State University, Tallahassee, FL, USA.2Institute of Molecular Biophysics, Florida State University, Tallahassee, FL, USA.3Biological Science Department, Florida State University, Tallahassee, FL, USA.4Department of Neuroscience, University of Utah, Salt Lake City, UT, USA |
Abstract
Glucagon-like peptide 1 (GLP-1) agonists provide strong therapeutic use to combat obesity, among a host of additional health-related benefits. Given that there is a GLP-1 signaling microcircuit in the olfactory bulb (OB), whose activation elicits a multiphasic response shaping mitral/tufted cell (M/TC) firing patterns, we examined the effect of semaglutide (sema) administration in mice. Fos2A-iCreER mice (TRAP2) mice were intraperitoneally injected with sema causing M/TC and granule (GCs) cells to be activated (TRAPPED), as well as anticipated neurons in the lateral hypothalamus (LH). FL-sema was used to map and determine access of the drug to the OB and the LH within 30 m – 4h. Specificity of binding was confirmed by substituting mice with targeted deletion of the GLP-1R. Next, mice lines in which odorant receptor (Olfr) 649 expressing mKate2 reporter were crossed with mice expressing genetically-encoded calcium reporter GCamp6f in M/TCs. These mice were maintained on control (CF) or moderately-high fat (MHF) diets, daily administered sema for one month or were isocalorically-restricted to the consumption of the drug-treated animal. Mice were surgically implanted with a cranial window to probe glomerular activity with valeric acid using an awake paradigm. Metabolically, sema caused abrupt weight loss that was proportionally congruent in both CF- and MHF-maintained mice. Weight loss that was driven by isocaloric restriction was gradual and stabilized to pre-restriction values when mice were removed from diet restriction, unlike sema-treated mice that rebounded to heavier body weights once removed from drug treatment. We are continuing analysis of glomerular activation to determine if it might be modulated by body weight changes induced by activation of GLP-1 signaling circuits.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
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