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We explored the role of\n                    <jats:italic>Gipr<\/jats:italic>\n                    neurons in the hypothalamus and dorsal vagal complex (DVC) \u2014 brain regions critical to the control of energy balance. Hypothalamic\n                    <jats:italic>Gipr<\/jats:italic>\n                    expression was not necessary for the synergistic effect of GIPR\/GLP-1R coagonism on body weight. While chemogenetic stimulation of both hypothalamic and DVC\n                    <jats:italic>Gipr<\/jats:italic>\n                    neurons suppressed food intake, activation of DVC\n                    <jats:italic>Gipr<\/jats:italic>\n                    neurons reduced ambulatory activity and induced conditioned taste avoidance, while there was no effect of a short-acting GIPR agonist (GIPRA). Within the DVC,\n                    <jats:italic>Gipr<\/jats:italic>\n                    neurons of the nucleus tractus solitarius (NTS), but not the area postrema (AP), projected to distal brain regions and were transcriptomically distinct. Peripherally dosed fluorescent GIPRAs revealed that access was restricted to circumventricular organs in the CNS. These data demonstrate that\n                    <jats:italic>Gipr<\/jats:italic>\n                    neurons in the hypothalamus, AP, and NTS differ in their connectivity, transcriptomic profile, peripheral accessibility, and appetite-controlling mechanisms. These results highlight the heterogeneity of the central GIPR signaling axis and suggest that studies into the effects of GIP pharmacology on feeding behavior should consider the interplay of multiple regulatory pathways.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.164921","type":"journal-article","created":{"date-parts":[[2023,5,21]],"date-time":"2023-05-21T14:00:56Z","timestamp":1684677656000},"source":"Crossref","is-referenced-by-count":81,"title":["Hypothalamic and brainstem glucose-dependent insulinotropic polypeptide receptor neurons employ distinct mechanisms to affect feeding"],"prefix":"10.1172","volume":"8","author":[{"given":"Alice","family":"Adriaenssens","sequence":"first","affiliation":[{"name":"Institute of Metabolic Science & MRC Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom."},{"name":"Department of Neuroscience, Physiology, and Pharmacology, University College London, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3084-6595","authenticated-orcid":true,"given":"Johannes","family":"Broichhagen","sequence":"additional","affiliation":[{"name":"Leibniz-Forschungsinstitut f\u00fcr Molekulare Pharmakologie (FMP), Berlin, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"de Bray","sequence":"additional","affiliation":[{"name":"Oxford Center for Diabetes, Endocrinology and Metabolism (OCDEM), NIHR Oxford Biomedical Research Center, Churchill Hospital, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom."},{"name":"Institute of Metabolism and Systems Research (IMSR) and Center of Membrane Proteins and Receptors (COMPARE), University of Birmingham, Birmingham, United 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