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

Curr Opin Clin Nutr Metab Care. 2009 Nov;12(6):601-6. doi: 10.1097/MCO.0b013e3283318a25.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic Agents / adverse effects
  • Adrenergic Agents / therapeutic use*
  • Animals
  • Cachexia / complications
  • Cachexia / drug therapy
  • Cachexia / metabolism
  • Humans
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / etiology
  • Muscular Atrophy / metabolism
  • Proteins / metabolism*
  • Receptors, Adrenergic, beta / metabolism*
  • Signal Transduction
  • Wasting Syndrome / drug therapy
  • Wasting Syndrome / metabolism*

Substances

  • Adrenergic Agents
  • Proteins
  • Receptors, Adrenergic, beta