{"doi":"10.1016/j.ebiom.2024.105283","title":"Regulator of G-protein signaling expression in human intestinal enteroendocrine cells and potential role in satiety hormone secretion in health and obesity","abstract":"BACKGROUND: Gut L-type enteroendocrine cells (EECs) are intestinal chemosensory cells that secrete satiety hormones GLP-1 and PYY in response to activation of G-protein coupled receptors (GPCRs) by luminal components of nutrient digestion and microbial fermentation. Regulator of G-protein Signaling (RGS) proteins are negative regulators of GPCR signaling. The expression profile of RGS in EECs, and their potential role in satiety hormone secretion and obesity is unknown. METHODS: Transcriptomic profiling of RGS was completed in native colonic EECs was completed using single-cell RNA sequencing (scRNA-Seq) in lean and obesity, and human jejunal EECs with data obtained from a publicly available RNAseq dataset (GSE114853). RGS validation studies were completed using whole mucosal intestinal tissue obtained during endoscopy in 61 patients (n = 42 OB, n = 19 Lean); a subset of patients' postprandial plasma was assayed for GLP-1 and PYY. Ex vivo human intestinal cultures and in vitro NCI-H716 cells overexpressing RGS9 were exposed to GLP-1 secretagogues in conjunction with a nonselective RGS-inhibitor and assayed for GLP-1 secretion. FINDINGS: Transcriptomic profiling of colonic and jejunal enteroendocrine cells revealed a unique RGS expression profile in EECs, and further within GLP-1+ L-type EECs. In obesity the RGS expression profile was altered in colonic EECs. Human gut RGS9 expression correlated positively with BMI and negatively with postprandial GLP-1 and PYY. RGS inhibition in human intestinal cultures increased GLP-1 release from EECs ex vivo. NCI-H716 cells overexpressing RGS9 displayed defective nutrient-stimulated GLP-1 secretion. INTERPRETATION: This study introduces the expression profile of RGS in human EECs, alterations in obesity, and suggests a role for RGS proteins as modulators of GLP-1 and PYY secretion from intestinal EECs. FUNDING: AA is supported by the NIH(C-Sig P30DK84567, K23 DK114460), a Pilot Award from the Mayo Clinic Center for Biomedical Discovery, and a Translational Product Development Fund from The Mayo Clinic Center for Clinical and Translational Science Office of Translational Practice in partnership with the University of Minnesota Clinical and Translational Science Institute.","journal":"EBioMedicine","year":2024,"id":443030,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9634,"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":379523,"name":"Alexander L. Ticho","orcid":"0000-0002-2115-010X","position":1,"is_corresponding":false},{"id":230193,"name":"Yuanhang Liu","orcid":"0000-0002-0147-8394","position":2,"is_corresponding":false},{"id":713237,"name":"Maria Laura Ricardo-Silgado","orcid":"0000-0002-0738-0523","position":3,"is_corresponding":false},{"id":1257670,"name":"Nothando N. Mangena","orcid":null,"position":4,"is_corresponding":false},{"id":1257671,"name":"Fauzi Feris Jassir","orcid":null,"position":5,"is_corresponding":false},{"id":915963,"name":"Daniel Gonzalez‐Izundegui","orcid":null,"position":6,"is_corresponding":false},{"id":623885,"name":"Gerardo Calderón","orcid":"0000-0003-0081-5376","position":7,"is_corresponding":false},{"id":947586,"name":"Fariborz Rakhshan Rohakhtar","orcid":null,"position":8,"is_corresponding":false},{"id":947587,"name":"Vernadette Simon","orcid":null,"position":9,"is_corresponding":false},{"id":648691,"name":"Ying Li","orcid":"0000-0002-9042-4768","position":10,"is_corresponding":false},{"id":328263,"name":"Cadman L. Leggett","orcid":"0000-0002-0495-3795","position":11,"is_corresponding":false},{"id":1257672,"name":"Daniela Hurtado","orcid":null,"position":12,"is_corresponding":false},{"id":404008,"name":"Nicholas F. LaRusso","orcid":"0000-0003-3266-0831","position":13,"is_corresponding":false},{"id":272307,"name":"Andrés Acosta","orcid":"0000-0003-2286-489X","position":14,"is_corresponding":false},{"id":1257181,"name":"Alison McRae","orcid":"0000-0001-9119-1110","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:01:24.471942Z","pmid":"39142076","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":[]}