{"doi":"10.1126/scitranslmed.adk4908","title":"<i>Glp1r-Lepr</i> coexpressing neurons modulate the suppression of food intake and body weight by a GLP-1/leptin dual agonist","abstract":"Glucagon-like peptide-1 (GLP-1) and leptin signal recent feeding and long-term energy stores, respectively, and play complementary roles in the modulation of energy balance. Previous work using single-cell techniques in mice revealed the existence of a population of leptin receptor ( Lepr )–containing dorsomedial hypothalamus (DMH) neurons marked by the expression of GLP-1 receptor ( Glp1r ; LepR Glp1r neurons) that play important roles in the control of feeding and body weight by leptin. Here, we demonstrate the existence of a population of LepR Glp1r neurons in the DMHs of nonhuman primates (NHPs), suggesting the potential translational relevance of these neurons. Consequently, we developed a GLP-1R/LepR dual agonist and demonstrated the physiological activity of both components in vivo using leptin-deficient and Lepr- deficient murine models. We further found roles for LepR Glp1r neurons in mediating the dual agonist’s efficacy on food intake and body weight loss. Ablating Lepr in Glp1r -expressing neurons (Lepr Glp1r KO mice) abrogated the suppression of food intake by the dual agonist. Furthermore, reactivation of Glp1r expression in Lepr neurons on an otherwise Glp1r -null background (Glp1r Lepr Re mice) was sufficient to permit the suppression of food intake and body weight by the dual agonist. Hence, LepR Glp1r neurons represent targets for a GLP-1R/LepR dual agonist that potently reduces food intake and body weight.","journal":"Science Translational Medicine","year":2024,"id":423153,"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":25,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"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":1180081,"name":"Kristine Deibler","orcid":"0000-0002-2376-8456","position":1,"is_corresponding":false},{"id":1218232,"name":"Wouter F. J. Hogendorf","orcid":"0000-0003-3231-5325","position":2,"is_corresponding":false},{"id":1218233,"name":"S. Sherona Bau","orcid":"0000-0002-2873-7974","position":3,"is_corresponding":false},{"id":1218234,"name":"Tine Glendorf","orcid":"0000-0002-6874-7405","position":4,"is_corresponding":false},{"id":1218235,"name":"Carsten E. Stidsen","orcid":"0000-0002-6636-3600","position":5,"is_corresponding":false},{"id":84964,"name":"Christian W. Tornøe","orcid":"0000-0002-6549-1213","position":6,"is_corresponding":false},{"id":1218863,"name":"Dong Tiantang","orcid":null,"position":7,"is_corresponding":false},{"id":1218236,"name":"Sofia Lundh","orcid":"0000-0002-4552-0312","position":8,"is_corresponding":false},{"id":347774,"name":"Charles Pyke","orcid":"0000-0002-7286-5009","position":9,"is_corresponding":false},{"id":407765,"name":"Abigail J. Tomlinson","orcid":"0000-0002-4192-9639","position":10,"is_corresponding":false},{"id":281133,"name":"Stace Kernodle","orcid":"0000-0001-7750-8804","position":11,"is_corresponding":false},{"id":1218864,"name":"I. Jack Magrisso","orcid":null,"position":12,"is_corresponding":false},{"id":1218237,"name":"Kilian W. Conde‐Frieboes","orcid":"0000-0001-5303-4448","position":13,"is_corresponding":false},{"id":268340,"name":"Martin G. Myers","orcid":"0000-0001-9468-2046","position":14,"is_corresponding":false},{"id":812165,"name":"Lotte Bjerre Knudsen","orcid":"0000-0002-2439-7116","position":15,"is_corresponding":false},{"id":107074,"name":"Randy J. Seeley","orcid":"0000-0002-3721-5625","position":16,"is_corresponding":false},{"id":1029278,"name":"Joseph Polex-Wolf","orcid":"0000-0002-0441-8872","position":0,"is_corresponding":true}],"reference_count":31,"raw_metadata":null,"created_at":"2026-07-19T01:57:56.814994Z","pmid":"39630884","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":[]}