Stimulation of the beta-2-adrenergic receptor with salbutamol activates human brown adipose tissue

Maaike E Straat; Carlijn A Hoekx; Floris H P van Velden; Lenka M Pereira Arias-Bouda; Lauralyne Dumont; Denis P Blondin; Mariëtte R Boon; Borja Martinez-Tellez; Patrick C N Rensen

doi:10.1016/j.xcrm.2023.100942

Stimulation of the beta-2-adrenergic receptor with salbutamol activates human brown adipose tissue

Cell Rep Med. 2023 Feb 21;4(2):100942. doi: 10.1016/j.xcrm.2023.100942.

Authors

Maaike E Straat¹, Carlijn A Hoekx¹, Floris H P van Velden², Lenka M Pereira Arias-Bouda², Lauralyne Dumont³, Denis P Blondin⁴, Mariëtte R Boon¹, Borja Martinez-Tellez¹, Patrick C N Rensen⁵

Affiliations

¹ Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands.
² Section of Nuclear Medicine, Department of Radiology, Leiden University Medical Center, 2333 ZA Leiden, the Netherlands.
³ Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada; Department of Physiology-Pharmacology, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
⁴ Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada; Department of Medicine, Division of Neurology, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada.
⁵ Division of Endocrinology, Department of Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, the Netherlands. Electronic address: p.c.n.rensen@lumc.nl.

Abstract

While brown adipose tissue (BAT) is activated by the beta-3-adrenergic receptor (ADRB3) in rodents, in human brown adipocytes, the ADRB2 is dominantly present and responsible for noradrenergic activation. Therefore, we performed a randomized double-blinded crossover trial in young lean men to compare the effects of single intravenous bolus of the ADRB2 agonist salbutamol without and with the ADRB1/2 antagonist propranolol on glucose uptake by BAT, assessed by dynamic 2-[¹⁸F]fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography scan (i.e., primary outcome). Salbutamol, compared with salbutamol with propranolol, increases glucose uptake by BAT, without affecting the glucose uptake by skeletal muscle and white adipose tissue. The salbutamol-induced glucose uptake by BAT positively associates with the increase in energy expenditure. Notably, participants with high salbutamol-induced glucose uptake by BAT have lower body fat mass, waist-hip ratio, and serum LDL-cholesterol concentration. In conclusion, specific ADRB2 agonism activates human BAT, which warrants investigation of ADRB2 activation in long-term studies (EudraCT: 2020-004059-34).

Keywords: brown fat; cardiometabolic diseases; energy expenditure; glucose metabolism; indirect calorimetry; lipoprotein metabolism; positron emission tomography; propranolol; responders.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adipose Tissue, Brown*
Albuterol* / pharmacology
Glucose / pharmacology
Humans
Male
Propranolol / pharmacology
Receptors, Adrenergic
Receptors, Adrenergic, beta-3

Substances

Albuterol
Propranolol
Glucose
Receptors, Adrenergic
ADRB3 protein, human
Receptors, Adrenergic, beta-3