{"doi":"10.1111/jne.12349","title":"Des‐Acyl Ghrelin Directly Targets the Arcuate Nucleus in a Ghrelin‐Receptor Independent Manner and Impairs the Orexigenic Effect of Ghrelin","abstract":"<jats:p>Ghrelin is a stomach‐derived octanoylated peptide hormone that plays a variety of well‐established biological roles acting via its specific receptor known as growth hormone secretagogue receptor (<jats:styled-content style=\"fixed-case\">GHSR</jats:styled-content>). In plasma, a des‐octanoylated form of ghrelin, named des‐acyl ghrelin (<jats:styled-content style=\"fixed-case\">DAG</jats:styled-content>), also exists. <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> is suggested to be a signalling molecule that has specific targets, including the brain, and regulates some physiological functions. However, no specific receptor for <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> has been reported until now, and, consequently, the potential role of <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> as a hormone has remained a matter of debate. In the present study, we show that <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> specifically binds to and acts on a subset of arcuate nucleus (<jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>) cells in a <jats:styled-content style=\"fixed-case\">GHSR</jats:styled-content>‐independent manner. <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content> cells labelled by a <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> fluorescent tracer include the neuropeptide Y (<jats:styled-content style=\"fixed-case\">NPY</jats:styled-content>) and non‐<jats:styled-content style=\"fixed-case\">NPY</jats:styled-content> neurones. Given the well‐established role of the <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content> in appetite regulation, we tested the effect of centrally administered <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> on food intake. We found that <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> failed to affect dark phase feeding, as well as food intake, after a starvation period; however, it impaired the orexigenic actions of peripherally administered ghrelin. Thus, we conclude that <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> directly targets <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content> neurones and antagonises the orexigenic effects of peripherally administered ghrelin.</jats:p>","journal":"Journal of Neuroendocrinology","year":2016,"id":633352,"datarank":0.6698862177981877,"base_score":4.465908118654584,"endowment":4.465908118654584,"self_citation_contribution":0.6698862177981877,"citation_network_contribution":0.0,"self_endowment_contribution":0.6698862177981877,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":86,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1642014,"name":"A. Cabral","orcid":null,"position":1,"is_corresponding":false},{"id":1642015,"name":"M. P. Cornejo","orcid":null,"position":2,"is_corresponding":false},{"id":1068798,"name":"Pablo N. De Francesco","orcid":"0000-0003-4226-7507","position":3,"is_corresponding":false},{"id":1642016,"name":"G. Garcia‐Romero","orcid":null,"position":4,"is_corresponding":false},{"id":1642017,"name":"M. Reynaldo","orcid":null,"position":5,"is_corresponding":false},{"id":1642018,"name":"M. Perello","orcid":null,"position":6,"is_corresponding":false},{"id":1642013,"name":"G. Fernandez","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Des‐Acyl Ghrelin Directly Targets the Arcuate Nucleus in a Ghrelin‐Receptor Independent Manner and Impairs the Orexigenic Effect of Ghrelin","abstract":"<jats:p>Ghrelin is a stomach‐derived octanoylated peptide hormone that plays a variety of well‐established biological roles acting via its specific receptor known as growth hormone secretagogue receptor (<jats:styled-content style=\"fixed-case\">GHSR</jats:styled-content>). In plasma, a des‐octanoylated form of ghrelin, named des‐acyl ghrelin (<jats:styled-content style=\"fixed-case\">DAG</jats:styled-content>), also exists. <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> is suggested to be a signalling molecule that has specific targets, including the brain, and regulates some physiological functions. However, no specific receptor for <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> has been reported until now, and, consequently, the potential role of <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> as a hormone has remained a matter of debate. In the present study, we show that <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> specifically binds to and acts on a subset of arcuate nucleus (<jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>) cells in a <jats:styled-content style=\"fixed-case\">GHSR</jats:styled-content>‐independent manner. <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content> cells labelled by a <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> fluorescent tracer include the neuropeptide Y (<jats:styled-content style=\"fixed-case\">NPY</jats:styled-content>) and non‐<jats:styled-content style=\"fixed-case\">NPY</jats:styled-content> neurones. Given the well‐established role of the <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content> in appetite regulation, we tested the effect of centrally administered <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> on food intake. We found that <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> failed to affect dark phase feeding, as well as food intake, after a starvation period; however, it impaired the orexigenic actions of peripherally administered ghrelin. Thus, we conclude that <jats:styled-content style=\"fixed-case\">DAG</jats:styled-content> directly targets <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content> neurones and antagonises the orexigenic effects of peripherally administered ghrelin.</jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26661382","pmcid":null,"openalex_id":null,"authors":[],"funders":[{"funder_name":"Consejo Nacional de Investigaciones Científicas y Técnicas","grant_id":"","title":null}],"total_grants":1,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"bronze","license":"cc-by-nc-sa","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jne.12349","host_type":"publisher"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fjne.12349","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jne.12349","host_type":"publisher"},{"url":"http://hdl.handle.net/11336/61685","host_type":"repository"}],"fields_of_study":[],"mesh_terms":["Neurons","Animals","Mice, Knockout","Injections, Subcutaneous","Eating","Ghrelin","Receptors, Ghrelin","Infusions, Intraventricular","Arcuate Nucleus of Hypothalamus"],"keywords":["Hypothalamus","food intake","Acyl-ghrelin","Des-acyl Ghrelin Receptor"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-06T11:54:55.458366Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}