{"doi":"10.1111/apha.14214","title":"Adipocyte endothelin B receptor activation inhibits adiponectin production and causes insulin resistance in obese mice","abstract":"Abstract Aims Endothelin‐1 (ET‐1) is elevated in patients with obesity and adipose tissue of obese mice fed high‐fat diet (HFD); however, its contribution to the pathophysiology of obesity is not fully understood. Genetic loss of endothelin type B receptors (ET B ) improves insulin sensitivity in rats and leads to increased circulating adiponectin, suggesting that ET B activation on adipocytes may contribute to obesity pathophysiology. We hypothesized that elevated ET‐1 in obesity promotes insulin resistance by reducing the secretion of insulin sensitizing adipokines, via ET B receptor. Methods Male adipocyte‐specific ET B receptor knockout (adET B KO), overexpression (adET B OX), or control littermates were fed either normal diet (NMD) or high‐fat diet (HFD) for 8 weeks. Results RNA‐sequencing of epididymal adipose (eWAT) indicated differential expression of over 5500 genes ( p < 0.05) in HFD compared to NMD controls, and changes in 1077 of these genes were attenuated in HFD adET B KO mice. KEGG analysis indicated significant increase in metabolic signaling pathway. HFD adET B KO mice had significantly improved glucose and insulin tolerance compared to HFD control. In addition, adET B KO attenuated changes in plasma adiponectin, insulin, and leptin that is observed in HFD versus NMD control mice. Treatment of primary adipocytes with ET‐1 caused a reduction in adiponectin production that was attenuated in cells pretreated with an ET B antagonist. Conclusion These data indicate elevated ET‐1 in adipose tissue of mice fed HFD inhibits adiponectin production and causes insulin resistance through activation of the ET B receptor on adipocytes.","journal":"Acta Physiologica","year":2024,"id":453123,"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":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9618,"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":1276102,"name":"Megumi F. Mills","orcid":null,"position":1,"is_corresponding":false},{"id":921077,"name":"Bridget Konadu","orcid":null,"position":2,"is_corresponding":false},{"id":1233179,"name":"Natalie Wilson","orcid":"0009-0000-1243-4429","position":3,"is_corresponding":false},{"id":704852,"name":"Hayley Murphy","orcid":"0009-0006-3074-3106","position":4,"is_corresponding":false},{"id":1276103,"name":"Madison Newberry","orcid":null,"position":5,"is_corresponding":false},{"id":260827,"name":"Kelly A. Hyndman","orcid":"0000-0002-8465-2588","position":6,"is_corresponding":false},{"id":321688,"name":"Michael R. Garrett","orcid":"0000-0001-5234-7928","position":7,"is_corresponding":false},{"id":1276104,"name":"David J. Webb","orcid":null,"position":8,"is_corresponding":false},{"id":351834,"name":"Joshua S. Speed","orcid":"0000-0002-0131-5253","position":9,"is_corresponding":false},{"id":352495,"name":"Osvaldo Rivera‐Gonzalez","orcid":null,"position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T02:02:58.784290Z","pmid":"39096077","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":[]}