TY - JOUR

T1 - The beta2-adrenergic receptor - a re-emerging target to combat obesity and induce leanness?

AU - Hostrup, Morten

AU - Onslev, Johan

N1 - This article is protected by copyright. All rights reserved.

PY - 2022

Y1 - 2022

N2 - Treatment of obesity with repurposed or novel drugs is an expanding research field. One approach is to target beta2-adrenergic receptors because they regulate the metabolism and phenotype of adipose and skeletal muscle tissue. Several observations support a role of the beta2-adrenergic receptor in obesity. Specific human beta2-adrenergic receptor polymorphisms are associated with body composition and obesity, for which the Gln27Glu polymorphism is associated with obesity, while the Arg16Gly polymorphism is associated with lean mass in men and the development of obesity in specific populations. Individuals with obesity also have lower abundancy of beta2-adrenergic receptors in adipose tissue and are less sensitive to catecholamines. In addition, studies in livestock and rodents demonstrate that selective beta2-agonists induce a so-called "repartitioning effect" characterized by muscle accretion and reduced fat deposition. In humans, beta2-agonists dose-dependently increase resting metabolic rate by 10-50%. And like that observed in other mammals, only a few weeks of treatment with beta2-agonists increases muscle mass and reduces fat mass in young healthy individuals. Beta2-agonists also exert beneficial effects on body composition when used concomitantly with training and work additively to increase muscle strength and mass during periods with resistance training. Thus, the beta2-adrenergic receptor seems like an attractive target in the development of anti-obesity drugs. However, future studies need to verify the long-term efficacy and safety of beta2-agonists in individuals with obesity, particularly in those with comorbidities.

AB - Treatment of obesity with repurposed or novel drugs is an expanding research field. One approach is to target beta2-adrenergic receptors because they regulate the metabolism and phenotype of adipose and skeletal muscle tissue. Several observations support a role of the beta2-adrenergic receptor in obesity. Specific human beta2-adrenergic receptor polymorphisms are associated with body composition and obesity, for which the Gln27Glu polymorphism is associated with obesity, while the Arg16Gly polymorphism is associated with lean mass in men and the development of obesity in specific populations. Individuals with obesity also have lower abundancy of beta2-adrenergic receptors in adipose tissue and are less sensitive to catecholamines. In addition, studies in livestock and rodents demonstrate that selective beta2-agonists induce a so-called "repartitioning effect" characterized by muscle accretion and reduced fat deposition. In humans, beta2-agonists dose-dependently increase resting metabolic rate by 10-50%. And like that observed in other mammals, only a few weeks of treatment with beta2-agonists increases muscle mass and reduces fat mass in young healthy individuals. Beta2-agonists also exert beneficial effects on body composition when used concomitantly with training and work additively to increase muscle strength and mass during periods with resistance training. Thus, the beta2-adrenergic receptor seems like an attractive target in the development of anti-obesity drugs. However, future studies need to verify the long-term efficacy and safety of beta2-agonists in individuals with obesity, particularly in those with comorbidities.

KW - Faculty of Science

KW - Thermogenesis

KW - Adrenoceptor

KW - Hypertrophy

KW - Beta agonist

KW - Clenbuterol

KW - Salbutamol

U2 - 10.1113/JP281819

DO - 10.1113/JP281819

M3 - Review

C2 - 34676534

VL - 600

SP - 1209

EP - 1227

JO - The Journal of Physiology

JF - The Journal of Physiology

SN - 0022-3751

IS - 5

ER -