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Nat Med:日本学者揭示肝荷尔蒙为何对运动减肥无效

摘要 : 2017年2月27日,国际学术权威刊物自然出版集团旗下子刊《Nature Medicine》杂志在线发表了日本金泽大学医学研究科Toshinari Takamura研究员的一篇研究论文,研究论文报道肝脏分泌的一种荷尔蒙作用于骨骼肌,会引起“运动抵抗性”的病态,导致运动效果差强人意。

 2017年2月27日,国际学术权威刊物自然出版集团旗下子刊《Nature Medicine》杂志在线发表了日本金泽大学大学院医学研究科Toshinari Takamura研究员的一篇研究论文,研究论文报道肝脏分泌的一种荷尔蒙作用于骨骼肌,会引起“运动抵抗性”的病态,导致运动效果差强人意。






Deficiency of the hepatokine selenoprotein P increases responsiveness to exercise in mice through upregulation of reactive oxygen species and AMP-activated protein kinase in muscle


Exercise has numerous health-promoting effects in humans1; however, individual responsiveness to exercise with regard to endurance or metabolic health differs markedly2, 3, 4. This 'exercise resistance' is considered to be congenital, with no evident acquired causative factors. Here we show that the anti-oxidative hepatokine selenoprotein P (SeP)5, 6, 7 causes exercise resistance through its muscle receptor low-density lipoprotein receptor–related protein 1 (LRP1)8. SeP-deficient mice showed a 'super-endurance' phenotype after exercise training, as well as enhanced reactive oxygen species (ROS) production, AMP-activated protein kinase (AMPK) phosphorylation9 and peroxisome proliferative activated receptor γ coactivator (Ppargc)-1α (also known as PGC-1α; encoded by Ppargc1a)10 expression in skeletal muscle. Supplementation with the anti-oxidant N-acetylcysteine (NAC) reduced ROS production and the endurance capacity in SeP-deficient mice. SeP treatment impaired hydrogen-peroxide-induced adaptations through LRP1 in cultured myotubes and suppressed exercise-induced AMPK phosphorylation and Ppargc1a gene expression in mouse skeletal muscle—effects which were blunted in mice with a muscle-specific LRP1 deficiency. Furthermore, we found that increased amounts of circulating SeP predicted the ineffectiveness of training on endurance capacity in humans. Our study suggests that inhibitors of the SeP–LRP1 axis may function as exercise-enhancing drugs to treat diseases associated with a sedentary lifestyle.

来源: Nature Medicine 浏览次数:0


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