{"doi":"10.1016/j.molmet.2020.02.012","title":"BRS3 in both MC4R- and SIM1-expressing neurons regulates energy homeostasis in mice","abstract":"OBJECTIVE: Bombesin-like receptor 3 (BRS3) is an orphan receptor and Brs3 knockout mice develop obesity with increased food intake and reduced resting metabolic rate and body temperature. The neuronal populations contributing to these effects were examined. METHODS: We studied energy metabolism in mice with Cre-mediated recombination causing 1) loss of BRS3 selectively in SIM1- or MC4R-expressing neurons or 2) selective re-expression of BRS3 from a null background in these neurons. RESULTS: The deletion of BRS3 in MC4R neurons increased body weight/adiposity, metabolic efficiency, and food intake, and reduced insulin sensitivity. BRS3 re-expression in these neurons caused partial or no reversal of these traits. However, these observations were confounded by an obesity phenotype caused by the Mc4r-Cre allele, independent of its recombinase activity. The deletion of BRS3 in SIM1 neurons increased body weight/adiposity and food intake, but not to the levels of the global null. The re-expression of BRS3 in SIM1 neurons reduced body weight/adiposity and food intake, but not to wild type levels. The deletion of BRS3 in either MC4R- or SIM1-expressing neurons affected body temperature, with re-expression in either population reversing the null phenotype. MK-5046, a BRS3 agonist, increases light phase body temperature in wild type, but not Brs3 null, mice and BRS3 re-expression in either population restored response to MK-5046. CONCLUSIONS: BRS3 in both MC4R- and SIM1-expressing neurons contributes to regulation of body weight/adiposity, insulin sensitivity, food intake, and body temperature.","journal":"Molecular Metabolism","year":2020,"id":69636,"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":20,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":253122,"name":"Naili Liu","orcid":null,"position":1,"is_corresponding":false},{"id":370257,"name":"Haley S. Province","orcid":null,"position":2,"is_corresponding":false},{"id":368915,"name":"Ramón A. Piñol","orcid":"0000-0002-8877-8444","position":3,"is_corresponding":false},{"id":251345,"name":"Oksana Gavrilova","orcid":"0000-0002-9310-1198","position":4,"is_corresponding":false},{"id":251346,"name":"Marc L. Reitman","orcid":"0000-0002-0426-9475","position":5,"is_corresponding":false},{"id":251343,"name":"Cuiying Xiao","orcid":"0000-0002-9370-1230","position":0,"is_corresponding":true}],"reference_count":64,"raw_metadata":null,"created_at":"2026-07-18T21:42:48.813846Z","pmid":"32229422","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":[]}