The role of beta-adrenoceptor signaling in skeletal muscle: therapeutic implications for muscle wasting disorders

PURPOSE OF REVIEW: The beta-adrenergic signaling pathway represents a novel therapeutic target for skeletal muscle wasting disorders due to its roles in regulating protein synthesis and degradation. beta-Adrenoceptor agonists (beta-agonists) have therapeutic potential for attenuating muscle wasting associated with sarcopenia (age-related muscle wasting), cancer cachexia, sepsis, disuse, burns, HIV-AIDS, chronic kidney or heart failure, and neuromuscular diseases such as the muscular dystrophies. This review describes the role of beta-adrenergic signaling in the mechanisms controlling muscle wasting due to its effects on protein synthesis, protein degradation, and muscle fiber phenotype. RECENT FINDINGS: Stimulation of the beta-adrenergic signaling pathway with beta-agonists has therapeutic potential for muscle wasting since administration can elicit an anabolic response in skeletal muscle. As a consequence of their potent muscle anabolic actions, the effects of beta-agonist administration have been examined in several animal models and human conditions of muscle wasting in the hope of discovering a new therapeutic. The repartitioning characteristics of beta-agonists (increasing muscle mass and decreasing fat mass) have also made them attractive anabolic agents for use in livestock and by some athletes. However, potentially deleterious cardiovascular side-effects of beta-agonists have been identified and these will need to be obviated in order for the therapeutic potential of beta-agonists to be realized. SUMMARY: Multiple studies have identified anticachectic effects of beta-agonists and their therapeutic potential for pathologic states when muscle protein hypercatabolism is indicated. Future studies examining beta-agonist administration for muscle wasting conditions need to separate beneficial effects on skeletal muscle from potentially deleterious effects on the heart and cardiovascular system.