Fenofibrate prevents skeletal muscle loss in mice with lung cancer Academic Article uri icon


MeSH Major

  • Cellular Reprogramming
  • Immunity
  • Interleukin-6
  • Pancreatic Neoplasms


  • The cancer anorexia cachexia syndrome is a systemic metabolic disorder characterized by the catabolism of stored nutrients in skeletal muscle and adipose tissue that is particularly prevalent in nonsmall cell lung cancer (NSCLC). Loss of skeletal muscle results in functional impairments and increased mortality. The aim of the present study was to characterize the changes in systemic metabolism in a genetically engineered mouse model of NSCLC. We show that a portion of these animals develop loss of skeletal muscle, loss of adipose tissue, and increased inflammatory markers mirroring the human cachexia syndrome. Using noncachexic and fasted animals as controls, we report a unique cachexia metabolite phenotype that includes the loss of peroxisome proliferator-activated receptor-α (PPARα) -dependent ketone production by the liver. In this setting, glucocorticoid levels rise and correlate with skeletal muscle degradation and hepatic markers of gluconeogenesis. Restoring ketone production using the PPARα agonist, fenofibrate, prevents the loss of skeletal muscle mass and body weight. These results demonstrate how targeting hepatic metabolism can prevent muscle wasting in lung cancer, and provide evidence for a therapeutic strategy.

publication date

  • January 23, 2018



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1073/pnas.1714703115

PubMed ID

  • 29311302

Additional Document Info

start page

  • E743

end page

  • E752


  • 115


  • 4