Hostrup Morten, Onslev Johan
Section of Integrative Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark.
J Physiol. 2022 Mar;600(5):1209-1227. doi: 10.1113/JP281819. Epub 2021 Nov 8.
Treatment of obesity with repurposed or novel drugs is an expanding research field. One approach is to target beta -adrenergic receptors because they regulate the metabolism and phenotype of adipose and skeletal muscle tissue. Several observations support a role for the beta -adrenergic receptor in obesity. Specific human beta -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 beta -adrenergic receptors in adipose tissue and are less sensitive to catecholamines. In addition, studies in livestock and rodents demonstrate that selective beta -agonists induce a so-called 'repartitioning effect' characterized by muscle accretion and reduced fat deposition. In humans, beta -agonists dose-dependently increase resting metabolic rate by 10-50%. And like that observed in other mammals, only a few weeks of treatment with beta -agonists increases muscle mass and reduces fat mass in young healthy individuals. Beta -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 beta -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 beta -agonists in individuals with obesity, particularly in those with comorbidities.
用重新利用或新型药物治疗肥胖是一个不断发展的研究领域。一种方法是靶向β-肾上腺素能受体，因为它们调节脂肪和骨骼肌组织的代谢及表型。多项观察结果支持β-肾上腺素能受体在肥胖中发挥作用。特定的人类β-肾上腺素能受体多态性与身体组成和肥胖相关，其中Gln27Glu多态性与肥胖相关，而Arg16Gly多态性与男性瘦体重及特定人群的肥胖发生相关。肥胖个体的脂肪组织中β-肾上腺素能受体丰度也较低，且对儿茶酚胺的敏感性较低。此外，对家畜和啮齿动物的研究表明，选择性β-激动剂会诱导一种所谓的“重新分配效应”，其特征为肌肉增加和脂肪沉积减少。在人类中，β-激动剂可使静息代谢率剂量依赖性地提高10%至50%。与在其他哺乳动物中观察到的情况一样，在年轻健康个体中，仅用几周的β-激动剂治疗就能增加肌肉量并减少脂肪量。β-激动剂与训练同时使用时，对身体组成也有有益影响，并且在进行抗阻训练期间可累加作用以增加肌肉力量和肌肉量。因此，β-肾上腺素能受体似乎是抗肥胖药物研发中一个有吸引力的靶点。然而，未来的研究需要验证β-激动剂对肥胖个体，尤其是对合并症患者的长期疗效和安全性。
