Preventive effects of electrical stimulation on inflammation-induced muscle mitochondrial dysfunction

Acta Histochem. 2016 Jun;118(5):464-70. doi: 10.1016/j.acthis.2016.04.011. Epub 2016 May 18.


Cachexia is a complex metabolic syndrome associated with underlying chronic diseases and is characterized by the overexpression of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), which impair muscle oxidative metabolism. We hypothesized that electrical stimulation (ES) would prevent decrement in muscle oxidative metabolism by suppressing the phosphorylation of p38 MAPK, a critical regulator of inflammatory response. Therefore, the purpose of the present study was to verify the effects of ES on inflammatory-induced decrement of oxidative metabolism in mice tibialis anterior muscles. ICR mice were randomly divided into three groups: control, lipopolysaccharide (LPS) injection for 4days, and LPS injection plus ES (LPS+ES). Cachexia was induced in the animals in the LPS groups via LPS injection (10mg/kg body weight/day, i.p.) during the intervention period. The animals in the LPS+ES group were stimulated electrically (carrier frequency, 2500Hz; modulation frequency, 100Hz; duration, 240s/day; type of contraction, isometric) during the intervention period. LPS injection resulted in decreased body and muscle wet weight and increased expression of TNF-α in plasma and skeletal muscle. In addition, LPS injection decreased indicators of mitochondrial function such as succinate dehydrogenase (SDH) and citrate synthase (CS) activity as well as the expression of PGC-1ɑ, and increased the phosphorylation of p38 MAPK. On the other hand, the intervention of ES attenuated the changes in muscle wet weight, SDH activity, CS activity, p38 MAPK, and PGC-1ɑ. These results suggest that ES could prevent decrement in muscle oxidative metabolism induced by pro-inflammatory cytokines in cachexia.

Keywords: Cachexia; Electrical stimulation; Lipopolysaccharide; Mitochondria; Skeletal muscle.

MeSH terms

  • Animals
  • Cachexia / blood
  • Cachexia / immunology
  • Cachexia / therapy
  • Citrate (si)-Synthase / metabolism
  • Electric Stimulation
  • Lipopolysaccharides / pharmacology
  • Male
  • Mice, Inbred ICR
  • Mitochondria, Muscle / immunology*
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Succinate Dehydrogenase / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Lipopolysaccharides
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, mouse
  • Tumor Necrosis Factor-alpha
  • Succinate Dehydrogenase
  • Citrate (si)-Synthase
  • p38 Mitogen-Activated Protein Kinases