Human Brown Adipocyte Thermogenesis Is Driven by beta 2-AR Stimulation

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Human Brown Adipocyte Thermogenesis Is Driven by beta 2-AR Stimulation. / Blondin, Denis P.; Nielsen, Søren; Kuipers, Eline N.; Severinsen, Mai C.; Jensen, Verena H.; Miard, Stephanie; Jespersen, Naja Z.; Kooijman, Sander; Boon, Mariette R.; Fortin, Melanie; Phoenix, Serge; Frisch, Frederique; Guerin, Brigitte; Turcotte, Eric E.; Haman, Francois; Richard, Denis; Picard, Frederic; Rensen, Patrick C. N.; Scheele, Camilla; Carpentier, Andre C.

In: Cell Metabolism, Vol. 32, No. 2, 2020, p. 287-300.e7.

Research output: Contribution to journal › Journal article › Research › peer-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, Guerin, B, Turcotte, EE, Haman, F, Richard, D, Picard, F, Rensen, PCN, Scheele, C & Carpentier, AC 2020, 'Human Brown Adipocyte Thermogenesis Is Driven by beta 2-AR Stimulation', Cell Metabolism, vol. 32, no. 2, pp. 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., Guerin, B., Turcotte, E. E., Haman, F., Richard, D., Picard, F., Rensen, P. C. N., Scheele, C., & Carpentier, A. C. (2020). Human Brown Adipocyte Thermogenesis Is Driven by beta 2-AR Stimulation. Cell Metabolism, 32(2), 287-300.e7. https://doi.org/10.1016/j.cmet.2020.07.005

Vancouver

Blondin DP, Nielsen S, Kuipers EN, Severinsen MC, Jensen VH, Miard S et al. Human Brown Adipocyte Thermogenesis Is Driven by beta 2-AR Stimulation. Cell Metabolism. 2020;32(2):287-300.e7. https://doi.org/10.1016/j.cmet.2020.07.005

Author

Blondin, Denis P. ; Nielsen, Søren ; Kuipers, Eline N. ; Severinsen, Mai C. ; Jensen, Verena H. ; Miard, Stephanie ; Jespersen, Naja Z. ; Kooijman, Sander ; Boon, Mariette R. ; Fortin, Melanie ; Phoenix, Serge ; Frisch, Frederique ; Guerin, Brigitte ; Turcotte, Eric E. ; Haman, Francois ; Richard, Denis ; Picard, Frederic ; Rensen, Patrick C. N. ; Scheele, Camilla ; Carpentier, Andre C. / Human Brown Adipocyte Thermogenesis Is Driven by beta 2-AR Stimulation. In: Cell Metabolism. 2020 ; Vol. 32, No. 2. pp. 287-300.e7.

Bibtex

@article{c1f6537b65f140ac86e4ef1a34cbd11f,
title = "Human Brown Adipocyte Thermogenesis Is Driven by beta 2-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 beta(3)-adrenergic receptor (beta(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 beta(3)-AR. Oral administration of the beta(3)-AR agonist mirabegron only elicited increases in BAT thermogenesis when ingested at the maximal allowable dose. This led to off-target binding to beta(1)-AR and beta(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 beta(2)-AR as well as knockdown of ADRB1, ADRB2, or ADRB3 in human brown adipocytes all confirmed that BAT lipolysis and thermogenesis occur through beta(2)-AR signaling in humans (ClinicalTrials.gov NCT02811289).",
keywords = "BETA-ADRENOCEPTOR AGONISTS, ADIPOSE-TISSUE, ENERGY-EXPENDITURE, BETA(3)-ADRENOCEPTOR AGONIST, OXIDATIVE-METABOLISM, MESSENGER-RNA, DOUBLE-BLIND, FATTY-ACID, COLD, RECEPTOR",
author = "Blondin, {Denis P.} and S{\o}ren Nielsen and Kuipers, {Eline N.} and Severinsen, {Mai C.} and Jensen, {Verena H.} and Stephanie Miard and Jespersen, {Naja Z.} and Sander Kooijman and Boon, {Mariette R.} and Melanie Fortin and Serge Phoenix and Frederique Frisch and Brigitte Guerin and Turcotte, {Eric E.} and Francois Haman and Denis Richard and Frederic Picard and Rensen, {Patrick C. N.} and Camilla Scheele and Carpentier, {Andre C.}",
year = "2020",
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 beta 2-AR Stimulation

AU - Blondin, Denis P.

AU - Nielsen, Søren

AU - Kuipers, Eline N.

AU - Severinsen, Mai C.

AU - Jensen, Verena H.

AU - Miard, Stephanie

AU - Jespersen, Naja Z.

AU - Kooijman, Sander

AU - Boon, Mariette R.

AU - Fortin, Melanie

AU - Phoenix, Serge

AU - Frisch, Frederique

AU - Guerin, Brigitte

AU - Turcotte, Eric E.

AU - Haman, Francois

AU - Richard, Denis

AU - Picard, Frederic

AU - Rensen, Patrick C. N.

AU - Scheele, Camilla

AU - Carpentier, Andre C.

PY - 2020

Y1 - 2020

N2 - Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the beta(3)-adrenergic receptor (beta(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 beta(3)-AR. Oral administration of the beta(3)-AR agonist mirabegron only elicited increases in BAT thermogenesis when ingested at the maximal allowable dose. This led to off-target binding to beta(1)-AR and beta(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 beta(2)-AR as well as knockdown of ADRB1, ADRB2, or ADRB3 in human brown adipocytes all confirmed that BAT lipolysis and thermogenesis occur through beta(2)-AR signaling in humans (ClinicalTrials.gov NCT02811289).

AB - Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the beta(3)-adrenergic receptor (beta(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 beta(3)-AR. Oral administration of the beta(3)-AR agonist mirabegron only elicited increases in BAT thermogenesis when ingested at the maximal allowable dose. This led to off-target binding to beta(1)-AR and beta(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 beta(2)-AR as well as knockdown of ADRB1, ADRB2, or ADRB3 in human brown adipocytes all confirmed that BAT lipolysis and thermogenesis occur through beta(2)-AR signaling in humans (ClinicalTrials.gov NCT02811289).

KW - BETA-ADRENOCEPTOR AGONISTS

KW - ADIPOSE-TISSUE

KW - ENERGY-EXPENDITURE

KW - BETA(3)-ADRENOCEPTOR AGONIST

KW - OXIDATIVE-METABOLISM

KW - MESSENGER-RNA

KW - DOUBLE-BLIND

KW - FATTY-ACID

KW - COLD

KW - RECEPTOR

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: 250118628