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The beta2‐adrenergic receptor – a re‐emerging target to combat obesity and induce leanness?

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 for 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 abundance 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 act 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.