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운동에 따른 골격근 AMPK 활성화에 있어서 Angptl4/Fiaf의 역할 : The Role for Angptl4/Fiaf in Exercise-Induced Skeletal Muscle AMPK Activation 원문보기

  • 저자

    신미선

  • 학위수여기관

    울산대학교

  • 학위구분

    국내박사

  • 학과

    의학과의학전공

  • 지도교수

    김민선

  • 발행년도

    2014

  • 총페이지

    40 p.

  • 키워드

    Angiopoietin-like protein 4 (Angptl4) AMP-activated protein kinase (AMPK) exercise muscle metabolism;

  • 언어

    eng

  • 원문 URL

    http://www.riss.kr/link?id=T13540403&outLink=K  

  • 초록

    BACKGROUND: Angiopoietin-like protein 4 (Angptl4), also known as the fasting-induced adipose factor (Fiaf), is a member of the angiopoietin-like protein family. Angptl4 has been implicated lipid and glucose metabolism in the adipose tissue and liver. In the hypothalamic neurons, Angptl4 regulates the AMP-activated protein kinase (AMPK) activity, through which it controls food intake and energy metabolism. AMPK is an important signaling molecule in integrating skeletal muscle metabolism during exercise, which helps to adapt skeletal muscle to exercise training. In my thesis, I investigated an involvement of Angptl4 in the exercise-induced AMPK activation in skeletal muscle. METHODS: Firstly, I investigated the effect of exercise on Angptl4 expression in leg skeletal muscles (gastrocnemius and soleus) of normal mice using immunoblotting. I next examined whether Angptl4 treatment induces an increase in the AMPK activity in C2C12 skeletal muscle cells by measuring the phosphorylation of AMPK and the acetyl-CoA carboxylase (ACC), a downstream molecular target of AMPK. Finally, I compared the ability to activate AMPK in leg skeletal muscle during treadmill exercise and the ability to endure swimming exercise between Angptl4 wild type and knockout mice. RESULTS: The protein and mRNA expression levels of Angptl4 were significantly increased in both gastrocnemius and soleus muscle in normal mice after 50 min of running exercise. Treatment of skeletal muscle cells with Angptl4 increased AMPK and ACC phosphorylation, which are markers of AMPK activity, in a dose- and time-dependent manner. Running exercise increased AMPK and ACC phosphorylation in the gastrocnemius muscle of wild type mice. These effects were attenuated in Angptl4 knockout mice. Exercise endurance was also reduced in Angptl4 knockout mice. CONCLUSIONS: I demonstrated that increased Angptl4 expression contributes to AMPK activation during exercise, which leads to increased exercise tolerability. These findings unveil a new physiological role for Angptl4 in skeletal muscle metabolism.


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