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研究発表を行った学会１； 第３５回日本分子生物学会年会
　２０１２年１２月１１日〜１４日（福岡）
研究発表を行った学会２； Ⅵ International Congress on Stress
Proteins in Biology and Medicine
　２０１３年　８月１８日〜２２日（Sheffield, UK）
タイトル；Mild electrical stimulation increases stress resistance and suppresses fat accumulation via activation of LKB1-AMPK signaling pathway.
発表者；松山　真吾　氏
　　　（熊本大学　大学院薬学教育部　遺伝子機能応用学分野）
Abstract；
Electrical current has been used as folk medicine and applied as treatment for various diseases. Previously, we showed that co-treatment of specific mild electrical stimulation (MES) and heat shock (HS) decreased fat accumulation and diabetic phenotypes in high fat-fed mice. Furthermore, pre-treatment with MES and HS prevented liver ischemia/reperfusion injury and gastric ulcer in mice. However, the mechanism responsible for the effects of MES are yet fully understood. Since MES affects metabolic phenotypes and stress response, we hypothesize that MES can potentially impact on AMPK signaling, whose defects has been implicated in the processes including metabolic dysfunction, cellular stress and damage. We first identified that MES (duration : 0.1 millisecond, number : 55 pulse per second, voltage : 1~2 V/cm) activates AMPK in skeletal muscle cell L6. MES-induced AMPK activation was suppressed in LKB1 inhibitor-treated and LKB1-deficient cells. MES also activated AMPK in wild-type N2 worms without affecting motor activity and feeding behavior, but not in the mutant worms of AMPK (gt33 and ok524) and LKB1 (it47 and it57). More interestingly, pre-treatment of N2 worms with MES suppressed fat accumulation and increased oxidative/heat stress resistance. Accordingly, MES suppressed the expression of lipogenic gene SREBP and increased the expression of anti-stress gene SODs and HSPs, β-oxidation related genes in wild-type worm despite no impact in AMPK- and LKB1-mutant worms. These results suggest that MES affects LKB1-AMPK signaling, which in turn suppresses fat accumulation and increases stress resistance via LKB1-AMPK in C. elegans.