{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T00:18:33Z","timestamp":1775866713584,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an effective therapeutic agent for obesity, primarily through its ability to suppress appetite and delay gastric emptying. However, the central neural substrates mediating its effects on food intake remain incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male mice received subcutaneous liraglutide injections in the cervical region to evalutates its effects on feeding behavior and body weight regulation. Retrograde transsynaptic tracing using pseudorabies virus (PRV) was employed to identify central amygdala (CeA) involvement in gastric-related neural circuits. The functional role of the CeA in feeding regulation was examined using chemogenetic and optogenetic activation, while local microinjection of GLP-1R agonists or antagonists into the CeA was used to evaluate receptor-specific effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Gastric wall injection of PRV anatomically revealed a direct connection between the stomach and the CeA. Site-specific administration of GLP-1R agonists into the CeA induced hypophagia and nausea-like behaviors in male mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides anatomical evidence that the CeA of male mice is involved in gastric regulatory circuits, and shows that the CeA responds to site-specific GLP-1R activation to induce hypophagia and nausea-like behaviors.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1740052","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T05:22:14Z","timestamp":1769577734000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Anatomical evidence links the stomach to the central amygdala, a region responsive to local GLP-1R agonist induced feeding and nausea-like behaviors in male mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Hui","family":"Yang","sequence":"first","affiliation":[{"name":"Institute of Neuroscience and Brain Diseases, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science","place":["Xiangyang, Hubei, China"]},{"name":"Department of Endocrinology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science","place":["Xiangyang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenxiang","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science","place":["Xiangyang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunling","family":"Gao","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Brain Diseases, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science","place":["Xiangyang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Brain Diseases, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science","place":["Xiangyang, Hubei, China"]},{"name":"Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine","place":["Shanghai, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaoyong","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Brain Diseases, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science","place":["Xiangyang, Hubei, China"]},{"name":"Department of Endocrinology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science","place":["Xiangyang, Hubei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(22)02403-5","article-title":"Contemporary medical, device, and surgical therapies for obesity in adults","volume":"401","author":"Perdomo","year":"2023","journal-title":"Lancet (London England)"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2023.03.002","article-title":"Global impact of obesity","volume":"52","author":"Alfaris","year":"2023","journal-title":"Gastroenterol Clinics North America"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.19897","article-title":"Obesity management in adults: A review","volume":"330","author":"Elmaleh-Sachs","year":"2023","journal-title":"Jama"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2024.10816","article-title":"Medications for obesity: A review","volume":"332","author":"Gudzune","year":"2024","journal-title":"Jama"},{"key":"B5","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s13578-022-00914-3","article-title":"Activation of arcuate nucleus glucagon-like peptide-1 receptor-expressing neurons suppresses food intake","volume":"12","author":"Singh","year":"2022","journal-title":"Cell bioscience"},{"key":"B6","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/j.cmet.2018.10.016","article-title":"Defined paraventricular hypothalamic populations exhibit differential responses to food contingent on caloric state","volume":"29","author":"Li","year":"2019","journal-title":"Cell Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2012.02364.x","article-title":"Vagal afferents mediate early satiation and prevent flavour avoidance learning in response to intraperitoneally infused exendin-4","volume":"24","author":"Labouesse","year":"2012","journal-title":"J Neuroendocrinol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07685-6","article-title":"Dissociable hindbrain GLP1R circuits for satiety and aversion","volume":"632","author":"Huang","year":"2024","journal-title":"Nature"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaf019","article-title":"Integration of glucagon-like peptide 1 receptor actions through the central amygdala","volume":"166","author":"Duran","year":"2025","journal-title":"Endocrinology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1017\/s0007114521002312","article-title":"Overview of the central amygdala role in feeding behaviour","volume":"127","author":"Izadi","year":"2022","journal-title":"Br J Nutr"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2019.03.002","article-title":"Inhibitory effects of peripheral administration of exendin-4 on food intake are attenuated by lesions of the central nucleus of amygdala","volume":"148","author":"Qiao","year":"2019","journal-title":"Brain Res Bull"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2021.724030","article-title":"Anatomical and functional characterization of central amygdala glucagon-like peptide 1 receptor expressing neurons","volume":"15","author":"Zeng","year":"2021","journal-title":"Front Behav Neurosci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.0528-24.2024","article-title":"Generation and characterization of a novel prkcd-cre rat model","volume":"44","author":"Toivainen","year":"2024","journal-title":"J Neurosci"},{"key":"B14","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1186\/s10194-022-01531-8","article-title":"CGRP-dependent sensitization of PKC-\u03b4 positive neurons in central amygdala mediates chronic migraine","volume":"23","author":"Chou","year":"2022","journal-title":"J headache Pain"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.2337\/db11-0464","article-title":"Brain GLP-1 signaling regulates femoral artery blood flow and insulin sensitivity through hypothalamic PKC-\u03b4","volume":"60","author":"Cabou","year":"2011","journal-title":"Diabetes"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0440-15.2015","article-title":"Glutamate receptors in the central nucleus of the amygdala mediate cisplatin-induced malaise and energy balance dysregulation through direct hindbrain projections","volume":"35","author":"Alhadeff","year":"2015","journal-title":"J Neurosci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3767","article-title":"Central amygdala PKC-\u03b4(+) neurons mediate the influence of multiple anorexigenic signals","volume":"17","author":"Cai","year":"2014","journal-title":"Nat Neurosci"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2023.1074979","article-title":"A central amygdala input to the dorsal vagal complex controls gastric motility in mice under restraint stress","volume":"14","author":"Wang","year":"2023","journal-title":"Front Physiol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e14498","DOI":"10.1111\/nmo.14498","article-title":"Regulation of the central amygdala on intestinal motility and behavior via the lateral hypothalamus in irritable bowel syndrome model mice","volume":"35","author":"He","year":"2023","journal-title":"Neurogastroenterol Motil"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e32799","DOI":"10.1371\/journal.pone.0032799","article-title":"Heat or insulation: behavioral titration of mouse preference for warmth or access to a nest","volume":"7","author":"Gaskill","year":"2012","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2015.10.031","article-title":"Hindbrain GLP-1 receptor mediation of cisplatin-induced anorexia and nausea","volume":"153","author":"De Jonghe","year":"2016","journal-title":"Physiol Behav"},{"key":"B22","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.neuron.2023.11.001","article-title":"An excitatory projection from the basal forebrain to the ventral tegmental area that underlies anorexia-like phenotypes","volume":"112","author":"Cai","year":"2024","journal-title":"Neuron"},{"key":"B23","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/j.cell.2018.08.049","article-title":"A neural circuit for gut-induced reward","volume":"175","author":"Han","year":"2018","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0256-4","article-title":"A corticopontine circuit for initiation of urination","volume":"21","author":"Yao","year":"2018","journal-title":"Nat Neurosci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.045906","article-title":"The central nucleus of the amygdala modulates gut-related neurons in the dorsal vagal complex in rats","volume":"553","author":"Zhang","year":"2003","journal-title":"J Physiol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"3395","DOI":"10.3390\/plants11233395","article-title":"Cisplatin-induced nausea and vomiting: effect of herbal medicines","volume":"11","author":"Shin","year":"2022","journal-title":"Plants (Basel Switzerland)"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/biom13020276","article-title":"Oxaliplatin-induced damage to the gastric innervation: role in nausea and vomiting","volume":"13","author":"Rahman","year":"2023","journal-title":"Biomolecules"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.133429","article-title":"Semaglutide lowers body weight in rodents via distributed neural pathways","volume":"5","author":"Gabery","year":"2020","journal-title":"JCI Insight"},{"key":"B29","doi-asserted-by":"publisher","first-page":"10310","DOI":"10.1038\/s41598-018-28496-6","article-title":"Integrated brain atlas for unbiased mapping of nervous system effects following liraglutide treatment","volume":"8","author":"Salinas","year":"2018","journal-title":"Sci Rep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173528","article-title":"GLP-1 receptors are involved in the GLP-1 (7-36) amide-induced modulation of glucose homoeostasis, emesis and feeding in Suncus murinus (house musk shrew)","volume":"888","author":"Lu","year":"2020","journal-title":"Eur J Pharmacol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/neurosci3040050","article-title":"Current Opinion on the Use of c-Fos in Neuroscience","volume":"3","author":"Lara Aparicio","year":"2022","journal-title":"NeuroSci"},{"key":"B32","doi-asserted-by":"publisher","first-page":"eadh0980","DOI":"10.1126\/sciadv.adh0980","article-title":"The locus coeruleus contributes to the anorectic, nausea, and autonomic physiological effects of glucagon-like peptide-1","volume":"9","author":"Fortin","year":"2023","journal-title":"Sci Adv"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/biof.1295","article-title":"Antiobesity efficacy of GLP-1 receptor agonist liraglutide is associated with peripheral tissue-specific modulation of lipid metabolic regulators","volume":"42","author":"Decara","year":"2016","journal-title":"BioFactors (Oxford England)"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1740052\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:13:54Z","timestamp":1771924434000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2026.1740052\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":33,"alternative-id":["10.3389\/fendo.2026.1740052"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2026.1740052","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,28]]},"article-number":"1740052"}}