Mild electrical stimulation increases stress resistance and suppresses fat accumulation via activation of LKB1-AMPK signaling pathway in C. elegans

PLoS One. 2014 Dec 9;9(12):e114690. doi: 10.1371/journal.pone.0114690. eCollection 2014.

Abstract

Electrical current at physiological strength has been applied as a therapeutic approach for various diseases. Several of our works showed that mild electrical stimulation (MES) at 0.1-ms pulse width has positive impact on organisms. But despite the growing evidence of the beneficial effects of MES, its effects on individual animals and the molecular underpinnings are poorly understood and rarely studied. Here, we examined the effects of MES on individual animal and its mechanisms by mainly using Caenorhabditis elegans, a powerful genetic model organism. Interestingly, MES increased stress resistance and suppressed excess fat accumulation in wild-type N2 worms but not in AMPK/AAK-2 and LKB1/PAR-4 mutant worms. MES promoted the nuclear localization of transcription factors DAF-16 and SKN-1 and consequently increased the expression of anti-stress genes, whereas MES inhibited the nuclear localization of SBP-1 and suppressed the expression of lipogenic genes. Moreover, we found that MES induced the activation of LKB1/PAR4-AMPK/AAK2 pathway in C. elegans and in several mammalian cell lines. The mitochondrial membrane potential and cellular ATP level were slightly and transiently decreased by MES leading to the activation of LKB1-AMPK signaling pathway. Together, we firstly and genetically demonstrated that MES exerts beneficial effects such as stress resistance and suppression of excess fat accumulation, via activation of LKB1-AMPK signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • AMP-Activated Protein Kinases / metabolism
  • AMP-Activated Protein Kinases / physiology*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Line
  • Cells, Cultured
  • Electric Stimulation*
  • Fats / metabolism
  • Heat-Shock Response
  • Humans
  • Membrane Potential, Mitochondrial
  • Mice
  • Oxidative Stress
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Rats
  • Satellite Cells, Skeletal Muscle
  • Signal Transduction*
  • Stress, Physiological*

Substances

  • Caenorhabditis elegans Proteins
  • Fats
  • Adenosine Triphosphate
  • PAR-3 protein, C elegans
  • Protein Serine-Threonine Kinases
  • AMP-Activated Protein Kinases

Grants and funding

Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan to H. Kai (#19390045); Japan Society for the Promotion of Science (JSPS) Program (Research Fellowships for Young Scientists) of Japan; Program for Leading Graduate Schools “HIGO (Health life science: Interdisciplinary and Glocal Oriented), MEXT of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.