title: Mild electrical stimulation increases stress resistance and suppresses fat accumulation via activation of LKB1-AMPK signaling pathway in C. elegans.
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.
authors.affiliation: Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Matsuyama
authors.affiliation: Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Moriuchi
authors.affiliation: Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Suico
authors.affiliation: Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Yano
authors.affiliation: Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Morino-Koga
authors.affiliation: Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shuto
authors.affiliation: Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto City, Japan.
authors.forename: Kunitoshi
authors.initials: K
authors.lastname: Yamanaka
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kondo
authors.affiliation: Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Araki
authors.affiliation: Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto City, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kai
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D004558:Electric Stimulation; D005223:Fats / Q000378:metabolism; D018869:Heat-Shock Response; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D051379:Mice; D018384:Oxidative Stress; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D032496:Satellite Cells, Skeletal Muscle; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D029742:Caenorhabditis elegans Proteins; D005223:Fats; D000255:Adenosine Triphosphate; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases