{"doi":"10.1126/science.adj2537","title":"GLP-1 increases preingestive satiation via hypothalamic circuits in mice and humans","abstract":"Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are effective antiobesity drugs. However, the precise central mechanisms of GLP-1RAs remain elusive. We administered GLP-1RAs to patients with obesity and observed a heightened sense of preingestive satiation. Analysis of human and mouse brain samples pinpointed GLP-1 receptor (GLP-1R) neurons in the dorsomedial hypothalamus (DMH) as candidates for encoding preingestive satiation. Optogenetic manipulation of DMH GLP-1R neurons caused satiation. Calcium imaging demonstrated that these neurons are actively involved in encoding preingestive satiation. GLP-1RA administration increased the activity of DMH GLP-1R neurons selectively during eating behavior. We further identified that an intricate interplay between DMH GLP-1R neurons and neuropeptide Y/agouti-related peptide neurons of the arcuate nucleus (ARC NPY/AgRP neurons) occurs to regulate food intake. Our findings reveal a hypothalamic mechanism through which GLP-1RAs control preingestive satiation, offering previously unexplored neural targets for obesity and metabolic diseases.","journal":"Science","year":2024,"id":416468,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":134,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9525,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1199828,"name":"Joon Seok Park","orcid":"0000-0002-1901-8097","position":2,"is_corresponding":false},{"id":634397,"name":"Eun‐Sang Hwang","orcid":"0000-0002-4298-5368","position":3,"is_corresponding":false},{"id":1199829,"name":"Min-Jung Park","orcid":"0000-0003-1638-3491","position":4,"is_corresponding":false},{"id":1199830,"name":"Hwa Yun Shin","orcid":"0009-0007-1929-938X","position":5,"is_corresponding":false},{"id":1199831,"name":"Young Hee Lee","orcid":"0000-0003-0633-9841","position":6,"is_corresponding":false},{"id":145864,"name":"Kyung Min Kim","orcid":null,"position":7,"is_corresponding":false},{"id":257962,"name":"Laurent Gautron","orcid":"0000-0003-3609-7441","position":9,"is_corresponding":false},{"id":877305,"name":"Elizabeth Godschall","orcid":"0000-0002-9719-5048","position":10,"is_corresponding":false},{"id":1200722,"name":"B Portillo","orcid":null,"position":11,"is_corresponding":false},{"id":1200723,"name":"Kyle Grose","orcid":null,"position":12,"is_corresponding":false},{"id":1200724,"name":"Sang-Ho Jung","orcid":null,"position":13,"is_corresponding":false},{"id":1200725,"name":"So Lin Baek","orcid":null,"position":14,"is_corresponding":false},{"id":1199832,"name":"Young Hyun Yun","orcid":"0000-0002-2747-9459","position":15,"is_corresponding":false},{"id":1200726,"name":"Doyeon Lee","orcid":null,"position":16,"is_corresponding":false},{"id":1200727,"name":"Eunseong Kim","orcid":null,"position":17,"is_corresponding":false},{"id":1200728,"name":"Jason Ajwani","orcid":null,"position":18,"is_corresponding":false},{"id":1199833,"name":"Seong Ho Yoo","orcid":"0000-0001-5294-0596","position":19,"is_corresponding":false},{"id":411671,"name":"Ali D. Güler","orcid":"0000-0001-8218-850X","position":20,"is_corresponding":false},{"id":356544,"name":"Kevin W. Williams","orcid":"0000-0002-8434-8658","position":21,"is_corresponding":false},{"id":379079,"name":"Hyung Jin Choi","orcid":"0000-0003-0593-6978","position":22,"is_corresponding":false},{"id":1199827,"name":"Kyu Sik Kim","orcid":"0000-0001-9983-8759","position":0,"is_corresponding":true}],"reference_count":48,"raw_metadata":null,"created_at":"2026-07-19T01:56:20.964471Z","pmid":"38935778","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":[]}