Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Harvard

Blondin, DP, Nielsen, S, Kuipers, EN, Severinsen, MC, Jensen, VH, Miard, S, Jespersen, NZ, Kooijman, S, Boon, MR, Fortin, M, Phoenix, S, Frisch, F, Guérin, B, Turcotte, ÉE, Haman, F, Richard, D, Picard, F, Rensen, PCN, Scheele, C & Carpentier, AC 2020, 'Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation', Cell Metabolism, bind 32, nr. 2, s. 287-300.e7. https://doi.org/10.1016/j.cmet.2020.07.005

APA

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. (2020). Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation. Cell Metabolism, 32(2), 287-300.e7. https://doi.org/10.1016/j.cmet.2020.07.005

CBE

Blondin DP, Nielsen S, Kuipers EN, Severinsen MC, Jensen VH, Miard S, Jespersen NZ, Kooijman S, Boon MR, Fortin M, Phoenix S, Frisch F, Guérin B, Turcotte ÉE, Haman F, Richard D, Picard F, Rensen PCN, Scheele C, Carpentier AC. 2020. Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation. Cell Metabolism. 32(2):287-300.e7. https://doi.org/10.1016/j.cmet.2020.07.005

MLA

Vancouver

Author

Blondin, Denis P ; Nielsen, Soren ; Kuipers, Eline N ; Severinsen, Mai C ; Jensen, Verena H ; Miard, Stéphanie ; Jespersen, Naja Z ; Kooijman, Sander ; Boon, Mariëtte R ; Fortin, Mélanie ; Phoenix, Serge ; Frisch, Frédérique ; Guérin, Brigitte ; Turcotte, Éric E ; Haman, François ; Richard, Denis ; Picard, Frédéric ; Rensen, Patrick C N ; Scheele, Camilla ; Carpentier, André C. / Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation. I: Cell Metabolism. 2020 ; Bind 32, Nr. 2. s. 287-300.e7.

Bibtex

@article{3231a761619b4007b111e31a683bd3b9,
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 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.gov NCT02811289). Blondin et al. reveal that therapeutic doses of the β 3-AR agonist mirabegron do not stimulate human BAT. Biopsies from participants show that the lack of effect may be explained by the absence of β 3-AR and primary expression of β 2-AR. In human brown adipocytes, β 2-AR agonism increases respiration, whereas pharmacological and genetic inhibition of β 2-AR decrease respiration. ",
keywords = "brown adipocyte, brown adipose tissue, cold-induced thermogenesis, energy metabolism, mirabegron, positron emission tomography, β -adrenergic receptor",
author = "Blondin, {Denis P} and Soren Nielsen and Kuipers, {Eline N} and Severinsen, {Mai C} and Jensen, {Verena H} and St{\'e}phanie Miard and Jespersen, {Naja Z} and Sander Kooijman and Boon, {Mari{\"e}tte R} and M{\'e}lanie Fortin and Serge Phoenix and Fr{\'e}d{\'e}rique Frisch and Brigitte Gu{\'e}rin and Turcotte, {{\'E}ric E} and Fran{\c c}ois Haman and Denis Richard and Fr{\'e}d{\'e}ric Picard and Rensen, {Patrick C N} and Camilla Scheele and Carpentier, {Andr{\'e} C}",
note = "Copyright {\textcopyright} 2020 Elsevier Inc. All rights reserved.",
year = "2020",
month = aug,
day = "4",
doi = "10.1016/j.cmet.2020.07.005",
language = "English",
volume = "32",
pages = "287--300.e7",
journal = "Cell Metabolism",
issn = "1550-4131",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation

AU - Blondin, Denis P

AU - Nielsen, Soren

AU - Kuipers, Eline N

AU - Severinsen, Mai C

AU - Jensen, Verena H

AU - Miard, Stéphanie

AU - Jespersen, Naja Z

AU - Kooijman, Sander

AU - Boon, Mariëtte R

AU - Fortin, Mélanie

AU - Phoenix, Serge

AU - Frisch, Frédérique

AU - Guérin, Brigitte

AU - Turcotte, Éric E

AU - Haman, François

AU - Richard, Denis

AU - Picard, Frédéric

AU - Rensen, Patrick C N

AU - Scheele, Camilla

AU - Carpentier, André C

N1 - Copyright © 2020 Elsevier Inc. All rights reserved.

PY - 2020/8/4

Y1 - 2020/8/4

N2 - 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.gov NCT02811289). Blondin et al. reveal that therapeutic doses of the β 3-AR agonist mirabegron do not stimulate human BAT. Biopsies from participants show that the lack of effect may be explained by the absence of β 3-AR and primary expression of β 2-AR. In human brown adipocytes, β 2-AR agonism increases respiration, whereas pharmacological and genetic inhibition of β 2-AR decrease respiration.

AB - 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.gov NCT02811289). Blondin et al. reveal that therapeutic doses of the β 3-AR agonist mirabegron do not stimulate human BAT. Biopsies from participants show that the lack of effect may be explained by the absence of β 3-AR and primary expression of β 2-AR. In human brown adipocytes, β 2-AR agonism increases respiration, whereas pharmacological and genetic inhibition of β 2-AR decrease respiration.

KW - brown adipocyte

KW - brown adipose tissue

KW - cold-induced thermogenesis

KW - energy metabolism

KW - mirabegron

KW - positron emission tomography

KW - β -adrenergic receptor

UR - http://www.scopus.com/inward/record.url?scp=85089022184&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2020.07.005

DO - 10.1016/j.cmet.2020.07.005

M3 - Journal article

C2 - 32755608

VL - 32

SP - 287-300.e7

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 2

ER -

ID: 60805730