{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T15:25:55Z","timestamp":1792596355666,"version":"4.5.0"},"reference-count":45,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T00:00:00Z","timestamp":1651449600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,7,1]]},"abstract":"<jats:p>The induction of nausea and emesis is a major barrier to maximizing the weight loss profile of obesity medications, and therefore, identifying mechanisms that improve tolerability could result in added therapeutic benefit. The development of peptide YY (PYY)-based approaches to treat obesity are no exception, as PYY receptor agonism is often accompanied by nausea and vomiting. Here, we sought to determine whether glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) agonism reduces PYY-induced nausea-like behavior in mice. We found that central and peripheral administration of a GIPR agonist reduced conditioned taste avoidance (CTA) without affecting hypophagia mediated by a PYY analog. The receptors for GIP and PYY (Gipr and Npy2r) were found to be expressed by the same neurons in the area postrema (AP), a brainstem nucleus involved in detecting aversive stimuli. Peripheral administration of a GIPR agonist induced neuronal activation (cFos) in the AP. Further, whole-brain cFos analyses indicated that PYY-induced CTA was associated with augmented neuronal activity in the parabrachial nucleus (PBN), a brainstem nucleus that relays aversive\/emetic signals to brain regions that control feeding behavior. Importantly, GIPR agonism reduced PYY-mediated neuronal activity in the PBN, providing a potential mechanistic explanation for how GIPR agonist treatment reduces PYY-induced nausea-like behavior. Together, the results of our study indicate a novel mechanism by which GIP-based therapeutics may have benefit in improving the tolerability of weight loss agents.<\/jats:p>","DOI":"10.2337\/db21-0848","type":"journal-article","created":{"date-parts":[[2022,5,2]],"date-time":"2022-05-02T09:13:31Z","timestamp":1651482811000},"page":"1410-1423","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":74,"title":["GIPR Agonism Inhibits PYY-Induced Nausea-Like Behavior"],"prefix":"10.2337","volume":"71","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9138-3091","authenticated-orcid":false,"given":"Ricardo J.","family":"Samms","sequence":"first","affiliation":[{"name":"1Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Cosgrove","sequence":"additional","affiliation":[{"name":"1Lilly Research Laboratories, Lilly Corporate Center, 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IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Dunbar","sequence":"additional","affiliation":[{"name":"1Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mridula","family":"Dogra","sequence":"additional","affiliation":[{"name":"1Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Alsina-Fernandez","sequence":"additional","affiliation":[{"name":"1Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tito","family":"Borner","sequence":"additional","affiliation":[{"name":"2Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"3Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart C.","family":"De Jonghe","sequence":"additional","affiliation":[{"name":"2Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"3Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9782-6551","authenticated-orcid":false,"given":"Matthew R.","family":"Hayes","sequence":"additional","affiliation":[{"name":"2Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA"},{"name":"3Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamer","family":"Coskun","sequence":"additional","affiliation":[{"name":"1Lilly Research Laboratories, Lilly Corporate 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