Journal article
RYGB Induces Vagal Sensory Neuropathy Characterized by Altered GLP1R Expression and Enhanced Exendin-4 Responsiveness in Male Mice
American journal of physiology: endocrinology and metabolism, Vol.330(1), pp.E114-E126
01/01/2026
DOI: 10.1152/ajpendo.00452.2025
PMCID: PMC12797217
PMID: 41385561
Abstract
The effects of Roux-en-Y gastric bypass (RYGB) on the gut-brain axis remain poorly understood. This study specifically explores phenotypic changes in vagal afferent neurons in male obese C57BL/6J mice following RYGB. Our results show that RYGB induced the expression of Activating Transcription Factor 3 (Atf3) mRNA-a well-established marker of axonal injury-in a subset of vagal sensory neurons. Additionally, RYGB led to a significant reduction in both the proportion of vagal afferents expressing the Glucagon-Like Peptide 1 Receptor (Glp1r) and the overall Glp1r mRNA levels in the nodose ganglion. Nerve transection experiments replicated these changes, suggesting that axonal injury alone may account for the observed phenotypic alterations in vagal afferent neurons following RYGB. Electrophysiological recordings further revealed that acute administration of exendin-4, a GLP1R agonist, significantly enhanced afferent vagus nerve firing. Interestingly, this response was notably exaggerated in RYGB animals and those with injured gastric vagus nerves. Collectively, these findings provide both molecular and electrophysiological evidence that RYGB induces vagal neuropathy, characterized by reduced Glp1r expression and heightened sensitivity to GLP1.
Details
- Title: Subtitle
- RYGB Induces Vagal Sensory Neuropathy Characterized by Altered GLP1R Expression and Enhanced Exendin-4 Responsiveness in Male Mice
- Creators
- Warda Merchant - Southwestern Medical CenterArely Salazar Tinajero - Southwestern Medical CenterAdan Khan - The University of Texas Southwestern Medical CenterYi Chu - University of IowaSanaz Saleh - University of IowaDana Tasabehji - University of IowaDonald A Morgan - University of IowaKevin W Williams - Southwestern Medical CenterKamal Rahmouni - Iowa City VA Health Care SystemMohamad Mokadem - Iowa City VA Health Care SystemLaurent Gautron - Southwestern Medical Center
- Resource Type
- Journal article
- Publication Details
- American journal of physiology: endocrinology and metabolism, Vol.330(1), pp.E114-E126
- DOI
- 10.1152/ajpendo.00452.2025
- PMID
- 41385561
- PMCID
- PMC12797217
- NLM abbreviation
- Am J Physiol Endocrinol Metab
- ISSN
- 1522-1555
- eISSN
- 1522-1555
- Publisher
- American Physiological Society; Rockville
- Grant note
- R01DK141541-01A1 / HHS | National Institutes of Health (NIH) P01DK119130 / HHS | NIH | NIDDK | Division of Diabetes, Endocrinology, and Metabolic Diseases (DEM) HL172944 / HHS | National Institutes of Health (NIH) I01 BX004774 / BLRD VA TRC4066 / University of Texas System (UT) HL162773 / HHS | National Institutes of Health (NIH) I01 BX004249 / BLRD VA IK6 BX006040 / BLRD VA
- Language
- English
- Electronic publication date
- 12/12/2025
- Date published
- 01/01/2026
- Academic Unit
- Gastroenterology and Hepatology; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
- Record Identifier
- 9985090600302771
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