{"doi":"10.1016/j.cmet.2020.07.005","title":"Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation","abstract":null,"journal":"Cell Metabolism","year":2020,"id":623879,"datarank":6.907947497870995,"base_score":5.802118375377063,"endowment":5.802118375377063,"self_citation_contribution":0.8703177563065596,"citation_network_contribution":6.0376297415644355,"self_endowment_contribution":0.8703177563065596,"citer_contribution":6.0376297415644355,"corpus_percentile":null,"corpus_rank":null,"citation_count":330,"citer_count":200,"citers_with_citation_signal":200,"citers_with_endowment":200,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1612542,"name":"Soren Nielsen","orcid":null,"position":1,"is_corresponding":false},{"id":630116,"name":"Eline N. Kuipers","orcid":"0000-0003-1360-7525","position":2,"is_corresponding":false},{"id":1612543,"name":"Mai C. Severinsen","orcid":null,"position":3,"is_corresponding":false},{"id":1612544,"name":"Verena H. Jensen","orcid":null,"position":4,"is_corresponding":false},{"id":668594,"name":"Stéphanie Miard","orcid":null,"position":5,"is_corresponding":false},{"id":1612545,"name":"Naja Z. Jespersen","orcid":null,"position":6,"is_corresponding":false},{"id":630114,"name":"Sander Kooijman","orcid":"0000-0002-0014-5571","position":7,"is_corresponding":false},{"id":1612546,"name":"Mariëtte R. Boon","orcid":null,"position":8,"is_corresponding":false},{"id":1587682,"name":"Mélanie Fortin","orcid":null,"position":9,"is_corresponding":false},{"id":1587683,"name":"Serge Phoenix","orcid":null,"position":10,"is_corresponding":false},{"id":668595,"name":"Frédérique Frisch","orcid":null,"position":11,"is_corresponding":false},{"id":1587685,"name":"Brigitte Guérin","orcid":null,"position":12,"is_corresponding":false},{"id":1587686,"name":"Éric E. Turcotte","orcid":null,"position":13,"is_corresponding":false},{"id":827773,"name":"François Haman","orcid":"0000-0002-3728-1665","position":14,"is_corresponding":false},{"id":667840,"name":"Denis Richard","orcid":"0000-0003-3995-0938","position":15,"is_corresponding":false},{"id":667842,"name":"Frédéric Picard","orcid":"0000-0003-4365-0743","position":16,"is_corresponding":false},{"id":611041,"name":"Patrick C.N. Rensen","orcid":"0000-0002-8455-4988","position":17,"is_corresponding":false},{"id":1612547,"name":"Camilla Scheele","orcid":null,"position":18,"is_corresponding":false},{"id":667841,"name":"André C. Carpentier","orcid":"0000-0002-3983-8156","position":19,"is_corresponding":false},{"id":827775,"name":"Denis P. Blondin","orcid":"0000-0001-6805-0985","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation","abstract":"Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the β<sub>3</sub>-adrenergic receptor (β<sub>3</sub>-AR), the adrenergic receptor believed to mediate BAT thermogenesis, have historically performed poorly in human clinical trials. Here we report that, in contrast to rodents, human BAT thermogenesis is not mediated by the stimulation of β<sub>3</sub>-AR. Oral administration of the β<sub>3</sub>-AR agonist mirabegron only elicited increases in BAT thermogenesis when ingested at the maximal allowable dose. This led to off-target binding to β<sub>1</sub>-AR and β<sub>2</sub>-AR, thereby increasing cardiovascular responses and white adipose tissue lipolysis, respectively. ADRB2 was co-expressed with UCP1 in human brown adipocytes. Pharmacological stimulation and inhibition of the β<sub>2</sub>-AR as well as knockdown of ADRB1, ADRB2, or ADRB3 in human brown adipocytes all confirmed that BAT lipolysis and thermogenesis occur through β<sub>2</sub>-AR signaling in humans (ClinicalTrials.govNCT02811289).","is_dataset_classified":null,"base_score":5.802118375377063,"endowment":5.802118375377063,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"32755608","pmcid":null,"openalex_id":"https://openalex.org/W3047205014","authors":[],"funders":[{"funder_name":"Danmarks Grundforskningsfond","grant_id":"DNRF55","title":null},{"funder_name":"Novo Nordisk Fonden","grant_id":"NNF18CC0034900","title":null},{"funder_name":"Diabetes Fonds","grant_id":"2015.81.1808","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"299962","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"PJT 159758","title":null},{"funder_name":"Canadian Institutes of Health Research","grant_id":"PJT 148550","title":null},{"funder_name":"Strategiske Forskningsråd","grant_id":"09-075724","title":null},{"funder_name":"Strategiske Forskningsråd","grant_id":"09-067009","title":null},{"funder_name":"Danish Diabetes Academy","grant_id":"PD007-18","title":null},{"funder_name":"TrygFonden","grant_id":"101390","title":null},{"funder_name":"TrygFonden","grant_id":"20045","title":null},{"funder_name":"Hartstichting","grant_id":"CVON2017-20","title":null},{"funder_name":"Hartstichting","grant_id":"2009T038","title":null},{"funder_name":"Novo Nordisk Fonden","grant_id":"NNF20OC0061400","title":null},{"funder_name":"NNF Center for Basic Metabolic Research","grant_id":"Schéele Group","title":null},{"funder_name":"Novo Nordisk Foundation","grant_id":"unidentified","title":"unidentified"},{"funder_name":"Novartis Pharmaceuticals Canada","grant_id":"","title":null},{"funder_name":"ZonMw","grant_id":"","title":null},{"funder_name":"HLS Therapeutics","grant_id":"","title":null},{"funder_name":"Eli Lilly and Company","grant_id":"","title":null},{"funder_name":"Centre Hospitalier Universitaire de Québec","grant_id":"","title":null},{"funder_name":"Fonds de Recherche du Québec - Santé","grant_id":"","title":null},{"funder_name":"Novo Nordisk Fonden","grant_id":"","title":null},{"funder_name":"Novo Nordisk Canada","grant_id":"","title":null}],"total_grants":24,"fwci":21.13,"citation_percentile":0.99706128,"influential_citations":0,"citation_trend":[{"year":2020,"count":8},{"year":2021,"count":63},{"year":2022,"count":57},{"year":2023,"count":59},{"year":2024,"count":60},{"year":2025,"count":50},{"year":2026,"count":32}],"oa_status":"bronze","license":"Elsevier Non-Commercial","oa_locations":[{"url":"http://www.cell.com/article/S1550413120303636/pdf","host_type":"journal"},{"url":"http://www.cell.com/article/S1550413120303636/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1550413120303636?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S1550413120303636?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.cmet.2020.07.005","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/32755608","host_type":"repository"},{"url":"http://hdl.handle.net/1887/3181350","host_type":"repository"},{"url":"https://researchprofiles.ku.dk/da/publications/c1f6537b-65f1-40ac-86e4-ef1a34cbd11f","host_type":"repository"},{"url":"https://hdl.handle.net/1887/3181350","host_type":"repository"},{"url":"https://dx.doi.org/10.1016/j.cmet.2020.07.005","host_type":""},{"url":"https://doi.org/https://doi.org/10.1016/j.cmet.2020.07.005","host_type":""}],"fields_of_study":["Adipose Tissue and Metabolism","Thermoregulation and physiological responses","Circadian rhythm and melatonin","0301 basic medicine","03 medical and health sciences","0303 health sciences","Adipocytes, Brown","Adolescent","Adult","Animals","Humans","Male","Mice","Mice, Inbred C57BL","Middle Aged","Receptors, Adrenergic, beta-2","Thermogenesis","Young Adult"],"mesh_terms":["Adolescent","Adult","Animals","Humans","Male","Mice, Inbred C57BL","Middle Aged","Receptors, Adrenergic, beta-2","Thermogenesis","Mice","Adipocytes, Brown","Young Adult"],"keywords":["Thermogenesis","Stimulation","Adipocyte","Brown adipose tissue","Biology","Endocrinology","Internal medicine","Neuroscience","Medicine","Adipose tissue","Energy metabolism","Positron emission tomography","Brown Adipocyte","Mirabegron","Β(2)-adrenergic Receptor","Cold-induced Thermogenesis","Adult","Male","Adolescent","DOUBLE-BLIND","Mice","Young Adult","Animals","Humans","BETA(3)-ADRENOCEPTOR AGONIST","COLD","BETA-ADRENOCEPTOR AGONISTS","FATTY-ACID","RECEPTOR","ENERGY-EXPENDITURE","OXIDATIVE-METABOLISM","Middle Aged","Mice, Inbred C57BL","ADIPOSE-TISSUE","Adipocytes, Brown","Receptors, Adrenergic, beta-2","MESSENGER-RNA"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. Good health"},{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-04T01:47:04.666958Z","pmid":null,"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":[]}