β-Hydroxy-β-methylbutyrate (HMB) prevents dexamethasone-induced myotube atrophy

Biochem Biophys Res Commun. 2012 Jul 13;423(4):739-43. doi: 10.1016/j.bbrc.2012.06.029. Epub 2012 Jun 13.

Abstract

High levels of glucocorticoids result in muscle wasting and weakness. β-hydroxy-β-methylbutyrate (HMB) attenuates the loss of muscle mass in various catabolic conditions but the influence of HMB on glucocorticoid-induced muscle atrophy is not known. We tested the hypothesis that HMB prevents dexamethasone-induced atrophy in cultured myotubes. Treatment of cultured L6 myotubes with dexamethasone resulted in increased protein degradation and expression of atrogin-1 and MuRF1, decreased protein synthesis and reduced myotube size. All of these effects of dexamethasone were attenuated by HMB. Additional experiments provided evidence that the inhibitory effects of HMB on dexamethasone-induced increase in protein degradation and decrease in protein synthesis were regulated by p38/MAPK- and PI3K/Akt-dependent cell signaling, respectively. The present results suggest that glucocorticoid-induced muscle wasting can be prevented by HMB.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects*
  • Cell Line
  • Dexamethasone / adverse effects*
  • Muscle Fibers, Skeletal / drug effects*
  • Muscle Fibers, Skeletal / metabolism
  • Muscle Fibers, Skeletal / pathology*
  • Muscle Proteins / metabolism
  • Muscle Weakness / chemically induced
  • Muscle Weakness / prevention & control
  • Muscular Atrophy / chemically induced*
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / prevention & control*
  • Protein Biosynthesis / drug effects
  • Proteolysis / drug effects
  • Rats
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Tripartite Motif Proteins
  • Ubiquitin-Protein Ligases / metabolism
  • Valerates / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Muscle Proteins
  • Tripartite Motif Proteins
  • Valerates
  • beta-hydroxyisovaleric acid
  • Dexamethasone
  • Fbxo32 protein, mouse
  • SKP Cullin F-Box Protein Ligases
  • Trim63 protein, mouse
  • Ubiquitin-Protein Ligases