{"doi":"10.1016/j.celrep.2023.112935","title":"Angiotensin AT1A receptor signal switching in Agouti-related peptide neurons mediates metabolic rate adaptation during obesity","abstract":"Resting metabolic rate (RMR) adaptation occurs during obesity and is hypothesized to contribute to failed weight management. Angiotensin II (Ang-II) type 1 (AT 1A ) receptors in Agouti-related peptide (AgRP) neurons contribute to the integrative control of RMR, and deletion of AT 1A from AgRP neurons causes RMR adaptation. Extracellular patch-clamp recordings identify distinct cellular responses of individual AgRP neurons from lean mice to Ang-II: no response, inhibition via AT 1A and Gαi, or stimulation via Ang-II type 2 (AT 2 ) receptors and Gαq. Following diet-induced obesity, a subset of Ang-II/AT 1A -inhibited AgRP neurons undergo a spontaneous G-protein \"signal switch,\" whereby AT 1A stop inhibiting the cell via Gαi and instead begin stimulating the cell via Gαq. DREADD-mediated activation of Gαi, but not Gαq, in AT 1A -expressing AgRP cells stimulates RMR in lean and obese mice. Thus, loss of AT 1A -Gαi coupling within the AT 1A -expressing AgRP neuron subtype represents a molecular mechanism contributing to RMR adaptation.","journal":"Cell Reports","year":2023,"id":344770,"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":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9578,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":256364,"name":"Yavuz Yavuz","orcid":"0000-0002-2211-9665","position":1,"is_corresponding":false},{"id":479059,"name":"Jingwei Jiang","orcid":"0000-0002-9163-3633","position":2,"is_corresponding":false},{"id":655032,"name":"Guorui Deng","orcid":"0000-0002-4629-7722","position":3,"is_corresponding":false},{"id":1001856,"name":"Natalia M. Mathieu","orcid":"0000-0003-4414-8798","position":4,"is_corresponding":false},{"id":978049,"name":"McKenzie L. Ritter","orcid":"0000-0001-9560-1316","position":5,"is_corresponding":false},{"id":978050,"name":"Megan Opichka","orcid":"0000-0002-2961-8977","position":6,"is_corresponding":false},{"id":370964,"name":"John J. Reho","orcid":"0000-0003-0981-3027","position":7,"is_corresponding":false},{"id":225472,"name":"John D. McCorvy","orcid":"0000-0001-7555-9413","position":8,"is_corresponding":false},{"id":490956,"name":"Pablo Nakagawa","orcid":"0000-0002-1887-7367","position":9,"is_corresponding":false},{"id":978051,"name":"Lisa L. Morselli","orcid":"0000-0003-0514-329X","position":10,"is_corresponding":false},{"id":827798,"name":"Gary Mouradian","orcid":"0000-0002-5038-2567","position":11,"is_corresponding":false},{"id":256367,"name":"Deniz Atasoy","orcid":"0000-0002-3325-8820","position":12,"is_corresponding":false},{"id":479060,"name":"Huxing Cui","orcid":"0000-0002-8627-8534","position":13,"is_corresponding":false},{"id":364389,"name":"Matthew R. Hodges","orcid":"0000-0002-1692-9055","position":14,"is_corresponding":false},{"id":446759,"name":"Curt D. Sigmund","orcid":"0000-0002-1453-0921","position":15,"is_corresponding":false},{"id":370966,"name":"Justin L. Grobe","orcid":"0000-0001-9737-0873","position":16,"is_corresponding":false},{"id":370963,"name":"Kirthikaa Balapattabi","orcid":"0000-0001-5455-6037","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T01:11:35.133818Z","pmid":"37540598","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":[]}