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Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation
Open accessAbstract
Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the β 3-adrenergic receptor (β 3-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 3-AR. Oral administration of the β 3-AR agonist mirabegron only elicited increases in BAT thermogenesis when ingested at the maximal allowable dose. This led to off-target binding to β 1-AR and β 2-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 2-AR as well as knockdown of ADRB1, ADRB2, or ADRB3 in human brown adipocytes all confirmed that BAT lipolysis and thermogenesis occur through β 2-AR signaling in humans (ClinicalTrials.govNCT02811289).
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“However, the rise in catecholamines during resistance training [188] should stimulate white adipose tissue lipolysis [183] and activate brown adipose tissue heat production [189], which will increase energy expenditure.”
From Effects of Skeletal Muscle Hypertrophy on Fat Mass and Glucose Homeostasis in Humans and Animals: A Narrative Review with Systematic Literature Search (2025) · cites this paper as [189]
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Metadata
- Authors
- Blondin, D. P., Nielsen, S., Kuipers, E. N., Severinsen, M. C., Jensen, V. H., Miard, S., Jespersen, N. Z., Kooijman, S., Boon, M. R., Fortin, M., Phoenix, S., Frisch, F., Guérin, B., Turcotte, É. E., Haman, F., Richard, D., Picard, F., Rensen, P. C. N., Scheele, C., & Carpentier, A. C.
- Affiliations
- Université de Sherbrooke (CA)
- Leiden University Medical Center (NL)
- University of Copenhagen (DK)
- Institut universitaire de cardiologie et de pneumologie de Québec (CA)
- Centre de recherche du CHUS (CA)
- University of Ottawa (CA)
- Corresponding author
- Scheele, Camilla
- Carpentier, André C.
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 32
- Issue
- 2
- Pages
- 287-300.e7
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W3047205014
- Cited by
- 331
- References
- 56
- Citations by year
- 2026: 43 · 2025: 48 · 2024: 57 · 2023: 59 · 2022: 54 · 2021: 61 · 2020: 8
- FWCI
- 27.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Novo Nordisk Canada
- Danmarks Grundforskningsfond (DNRF55)
- Novo Nordisk Fonden (NNF18CC0034900)
- Diabetes Fonds (2015.81.1808)
- Centre Hospitalier Universitaire de Québec
- Canadian Institutes of Health Research (299962, PJT 159758, PJT 148550)
- Novartis Pharmaceuticals Canada
- HLS Therapeutics
- Eli Lilly and Company
- Københavns Universitet
- Fonds de Recherche du Québec - Santé
- Strategiske Forskningsråd (09-075724, 09-067009)
- Danish Diabetes Academy (PD007-18)
- TrygFonden (101390, 20045)
- ZonMw
- Hartstichting (CVON2017-20, 2009T038)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- brown adipocytes, thermogenesis, beta2-adrenergic receptor, cold acclimation
- MeSH terms
- Adolescent, Adult, Animals, Humans, Male, Mice, Inbred C57BL, Middle Aged, Receptors, Adrenergic, beta-2, Thermogenesis, Mice, Adipocytes, Brown, Young Adult
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