{"doi":"10.1111/jne.12168","title":"Divergent Neuronal Circuitries Underlying Acute Orexigenic Effects of Peripheral or Central Ghrelin: Critical Role of Brain Accessibility","abstract":"<jats:p>\n                    Ghrelin is an octanoylated peptide hormone that potently and rapidly increases food intake. The orexigenic action of ghrelin involves the hypothalamic arcuate nucleus (\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    ), which is accessible to plasma ghrelin and expresses high levels of the ghrelin receptor. Local administration of ghrelin in a variety of other brain nuclei also increases food intake. It is currently unclear, however, whether these non‐\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    ghrelin brain targets are impacted by physiological increases of plasma ghrelin. Thus, the present study aimed to clarify which ghrelin brain targets participate in the short‐term orexigenic actions of ghrelin. First, c‐Fos induction into mouse brains centrally or peripherally treated with ghrelin was analysed. It was confirmed that peripherally administered ghrelin dose‐dependently increases food intake and mainly activates c‐Fos in\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    neurones. By contrast, centrally administered ghrelin activates c‐Fos in a larger number of brain nuclei. To determine which nuclei are directly accessible to ghrelin, mice were centrally or peripherally injected with a fluorescent ghrelin tracer. It was found that peripherally injected tracer mainly accesses the\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    , whereas centrally injected tracer reaches most brain areas known to express ghrelin receptors. Subsequently, the effects of ghrelin were tested in\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    ‐ablated mice and it was found that these mice failed to increase food intake in response to peripherally administered ghrelin but fully responded to centrally administered ghrelin.\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    ‐ablated mice showed patterns of ghrelin‐induced c‐Fos expression similar to those seen in control mice with the exception of the\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    , where no c‐Fos was found. Thus, peripheral ghrelin mainly accesses the\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    , which is required for the orexigenic effects of the hormone. Central ghrelin accesses a variety of nuclei, which can mediate the orexigenic effects of the hormone, even in the absence of an intact\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    .\n                  </jats:p>","journal":"Journal of Neuroendocrinology","year":2014,"id":677157,"datarank":0.6995158641168101,"base_score":4.663439094112067,"endowment":4.663439094112067,"self_citation_contribution":0.6995158641168101,"citation_network_contribution":0.0,"self_endowment_contribution":0.6995158641168101,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":105,"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":1769295,"name":"S. Valdivia","orcid":null,"position":1,"is_corresponding":false},{"id":1642013,"name":"G. Fernandez","orcid":null,"position":2,"is_corresponding":false},{"id":1642017,"name":"M. Reynaldo","orcid":null,"position":3,"is_corresponding":false},{"id":1642018,"name":"M. Perello","orcid":null,"position":4,"is_corresponding":false},{"id":1642014,"name":"A. Cabral","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Divergent Neuronal Circuitries Underlying Acute Orexigenic Effects of Peripheral or Central Ghrelin: Critical Role of Brain Accessibility","abstract":"<jats:p>\n                    Ghrelin is an octanoylated peptide hormone that potently and rapidly increases food intake. The orexigenic action of ghrelin involves the hypothalamic arcuate nucleus (\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    ), which is accessible to plasma ghrelin and expresses high levels of the ghrelin receptor. Local administration of ghrelin in a variety of other brain nuclei also increases food intake. It is currently unclear, however, whether these non‐\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    ghrelin brain targets are impacted by physiological increases of plasma ghrelin. Thus, the present study aimed to clarify which ghrelin brain targets participate in the short‐term orexigenic actions of ghrelin. First, c‐Fos induction into mouse brains centrally or peripherally treated with ghrelin was analysed. It was confirmed that peripherally administered ghrelin dose‐dependently increases food intake and mainly activates c‐Fos in\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    neurones. By contrast, centrally administered ghrelin activates c‐Fos in a larger number of brain nuclei. To determine which nuclei are directly accessible to ghrelin, mice were centrally or peripherally injected with a fluorescent ghrelin tracer. It was found that peripherally injected tracer mainly accesses the\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    , whereas centrally injected tracer reaches most brain areas known to express ghrelin receptors. Subsequently, the effects of ghrelin were tested in\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    ‐ablated mice and it was found that these mice failed to increase food intake in response to peripherally administered ghrelin but fully responded to centrally administered ghrelin.\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    ‐ablated mice showed patterns of ghrelin‐induced c‐Fos expression similar to those seen in control mice with the exception of the\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    , where no c‐Fos was found. Thus, peripheral ghrelin mainly accesses the\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    , which is required for the orexigenic effects of the hormone. Central ghrelin accesses a variety of nuclei, which can mediate the orexigenic effects of the hormone, even in the absence of an intact\n                    <jats:styled-content style=\"fixed-case\">ARC</jats:styled-content>\n                    .\n                  </jats:p>","is_dataset_classified":null,"base_score":4.663439094112067,"endowment":4.663439094112067,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24888783","pmcid":"PMC4108543","openalex_id":"https://openalex.org/W2019654241","authors":[],"funders":[{"funder_name":"National Agency of Scientific and Technological Promotion of Argentina","grant_id":"PICT2010-1954","title":null},{"funder_name":"National Agency of Scientific and Technological Promotion of Argentina","grant_id":"PICT2011-2142","title":null},{"funder_name":"NIH","grant_id":"R03TW008925-01A1","title":null},{"funder_name":"FIC NIH HHS","grant_id":"R03 TW008925","title":null},{"funder_name":"Scientific Research Commission, Province of Buenos Aires","grant_id":"","title":null},{"funder_name":"CONICET","grant_id":"","title":null}],"total_grants":6,"fwci":3.6231,"citation_percentile":0.93901329,"influential_citations":0,"citation_trend":[{"year":2014,"count":2},{"year":2015,"count":11},{"year":2016,"count":7},{"year":2017,"count":10},{"year":2018,"count":8},{"year":2019,"count":13},{"year":2020,"count":10},{"year":2021,"count":10},{"year":2022,"count":9},{"year":2023,"count":6},{"year":2024,"count":10},{"year":2025,"count":5},{"year":2026,"count":4}],"oa_status":"green","license":"cc-by-nc-sa","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4108543","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4108543","host_type":"repository"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fjne.12168","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/jne.12168","host_type":"publisher"},{"url":"https://doi.org/10.1111/jne.12168","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24888783","host_type":"repository"},{"url":"http://hdl.handle.net/11336/33222","host_type":"repository"}],"fields_of_study":["Regulation of Appetite and Obesity","Biochemical Analysis and Sensing Techniques","Adipose Tissue and Metabolism","Animals","Arcuate Nucleus of Hypothalamus","Brain","Dose-Response Relationship, Drug","Eating","Ghrelin","Infusions, Intraventricular","Injections, Subcutaneous","Male","Mice","Microinjections","Neurons","Proto-Oncogene Proteins c-fos"],"mesh_terms":["Animals","Arcuate Nucleus of Hypothalamus","Brain","Dose-Response Relationship, Drug","Eating","Injections, Subcutaneous","Male","Microinjections","Neurons","Proto-Oncogene Proteins c-fos","Mice","Ghrelin","Infusions, Intraventricular"],"keywords":["Ghrelin","Orexigenic","Endocrinology","Internal medicine","Arc (geometry)","Hypothalamus","Arcuate nucleus","Receptor","Chemistry","Biology","Neuropeptide Y receptor","Neuropeptide","Medicine","monosodium glutamate","Dorsal vagal complex"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T03:42:26.454000Z","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":[]}