{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:46:45Z","timestamp":1787021205597,"version":"build-2736575974"},"reference-count":61,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FAPESP\/Brazil","award":["2020\/01318-8"],"award-info":[{"award-number":["2020\/01318-8"]}]},{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT2019-3054"],"award-info":[{"award-number":["PICT2019-3054"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT2020-3270"],"award-info":[{"award-number":["PICT2020-3270"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ghrelin acts via the growth hormone secretagogue receptor (GHSR) and increases both food intake and growth hormone (GH) secretion. Studies in mice with genetic manipulations of GH receptor (GHR) revealed that GH action is required for ghrelin's orexigenic effects. However, the biological basis of this interdependence remains unclear. Here, we studied the mechanisms by which GHR contributes to ghrelin-induced hyperphagia in male mice. Transcriptomic analyses of single-cell datasets revealed that Ghr and Ghsr are co-expressed in a small subset of neurons, particularly within the hypothalamic arcuate nucleus (ARH). Systemic ghrelin administration increased food intake, circulating GH, and glycemia but did not induce GHR activation in the brain, as indicated by the absence of pSTAT5 immunoreactivity. Central GH administration failed to enhance ghrelin-induced food intake or glycemia. To evaluate the role of peripheral GHR signaling, we treated mice with the brain-impermeable GHR antagonist pegvisomant. Systemically injected pegvisomant impaired ghrelin's orexigenic effect without affecting its impact on glycemia or hypothalamic c-Fos activation, indicating that peripheral GHR signaling is required for ghrelin-induced hyperphagia. Pegvisomant did not alter refeeding-induced or AgRP neuron-mediated hyperphagia, suggesting a selective blockade of ghrelin's action. Moreover, ghrelin-induced food intake was preserved in hepatocyte-specific GHR knockout mice, despite disrupted hepatic GH signaling. Thus, peripheral, non-hepatic GHR signaling is selectively required for the orexigenic effects of ghrelin. This work reveals a critical GH-dependent, liver-independent mechanism underlying ghrelin-driven feeding, with potential implications for the neuroendocrine regulation of appetite and for therapeutic strategies targeting the ghrelin\u2013GH axis in metabolic diseases.<\/jats:p>","DOI":"10.1210\/endocr\/bqag008","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T12:50:55Z","timestamp":1768481455000},"source":"Crossref","is-referenced-by-count":2,"title":["Ghrelin-induced food intake in male mice requires peripheral extrahepatic GHR signaling"],"prefix":"10.1210","volume":"167","author":[{"given":"Franco","family":"Barrile","sequence":"first","affiliation":[{"name":"Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology , La Plata, BA 1900 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5425-1946","authenticated-orcid":false,"given":"Mar\u00eda Paula","family":"Cornejo","sequence":"additional","affiliation":[{"name":"Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology , La Plata, BA 1900 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo N","family":"De Francesco","sequence":"additional","affiliation":[{"name":"Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology , La Plata, BA 1900 ,","place":["Argentina"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel O","family":"de Souza","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Biof\u00edsica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo , Sao Paulo 05508000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Willian O","family":"dos Santos","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Biof\u00edsica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo , Sao Paulo 05508000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick","family":"Wasinski","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Biof\u00edsica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo , Sao Paulo 05508000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"Kopchick","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Aging, Heritage College of Osteopathic Medicine, Ohio University , Athens, OH 45701 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4166-7608","authenticated-orcid":false,"suffix":"Jr","given":"Jose","family":"Donato","sequence":"additional","affiliation":[{"name":"Departamento de Fisiologia e Biof\u00edsica, Instituto de Ciencias Biomedicas, Universidade de Sao Paulo , Sao Paulo 05508000 ,","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2114-6765","authenticated-orcid":false,"given":"Mario","family":"Perell\u00f3","sequence":"additional","affiliation":[{"name":"Laboratory of Neurophysiology, Multidisciplinary Institute of Cell Biology , La Plata, BA 1900 ,","place":["Argentina"]},{"name":"Department of Surgical Sciences, Functional Pharmacology and Neuroscience, University of Uppsala , Uppsala 75312 ,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"issue":"2","key":"2026013002415469900_bqag008-B1","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1002\/j.2040-4603.2016.tb00692.x","article-title":"Neuroendocrine regulation of growth hormone secretion","volume":"6","author":"Steyn","year":"2016","journal-title":"Compr 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