Myostatin inhibitor YK11 as a preventative health supplement for bacterial sepsis

Biochem Biophys Res Commun. 2021 Mar 5:543:1-7. doi: 10.1016/j.bbrc.2021.01.030. Epub 2021 Feb 12.


Muscle wasting caused by catabolic reactions in skeletal muscle is commonly observed in patients with sepsis. Myostatin, a negative regulator of muscle mass, has been reported to be upregulated in diseases associated with muscle atrophy. However, the behavior of myostatin during sepsis is not well understood. Herein, we sought to investigate the expression and regulation of myostatin in skeletal muscle in mice inoculated with gram-negative bacteria. Interestingly, the protein level of myostatin was found to increase in the muscle of septic mice simultaneously with an increase in the levels of follistatin, NF-κΒ, myogenin, MyoD, p- FOXO3a, and p-Smad2. Furthermore, the inhibition of myostatin by YK11 repressed the levels of pro-inflammatory cytokines and organ damage markers in the bloodstream and in the major organs of mice, which originally increased in sepsis; thus, myostatin inhibition by YK11 decreased the mortality rate due to sepsis. The results of this study suggest that YK11 may help revert muscle wasting during sepsis and subdue the inflammatory environment, thereby highlighting its potential as a preventive agent for sepsis-related muscle wasting.

Keywords: Follistatin; Muscle atrophy; Myostatin; Sepsis; YK11.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cachexia / metabolism
  • Cachexia / pathology
  • Cachexia / prevention & control
  • Cytokines / metabolism
  • Disease Models, Animal
  • Escherichia coli / drug effects*
  • Escherichia coli Infections / drug therapy*
  • Escherichia coli Infections / metabolism
  • Escherichia coli Infections / microbiology
  • Male
  • Mice
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / metabolism
  • Muscular Atrophy / pathology
  • Muscular Atrophy / prevention & control*
  • Myostatin / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Norpregnadienes / pharmacology*
  • Sepsis / drug therapy*
  • Sepsis / metabolism
  • Sepsis / pathology


  • 17,20-((1-methoxyethylidene)bis(oxy))-3-oxo-19-norpregna-4,20-diene-21-carboxylic acid methyl ester
  • Cytokines
  • Myostatin
  • NF-kappa B
  • Norpregnadienes