Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis.
Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis.
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DOI：
10.1038/nature10758
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发表时间：
2012-01-18
期刊：
影响因子：
64.8
通讯作者：
Levine, Beth
中科院分区：
文献类型：
--
作者：
He, Congcong;Bassik, Michael C.;Moresi, Viviana;Sun, Kai;Wei, Yongjie;Zou, Zhongju;An, Zhenyi;Loh, Joy;Fisher, Jill;Sun, Qihua;Korsmeyer, Stanley;Packer, Milton;May, Herman I.;Hill, Joseph A.;Virgin, Herbert W.;Gilpin, Christopher;Xiao, Guanghua;Bassel-Duby, Rhonda;Scherer, Philipp E.;Levine, Beth
运动对人体健康有益，包括预防糖尿病等代谢紊乱。然而，这些影响的细胞机制尚未完全了解。溶酶体降解途径，自噬，是一种细胞内循环系统，在细胞器和蛋白质质量控制的基础条件下发挥作用。在应激期间，自噬水平的增加允许细胞通过蛋白质催化剂适应不断变化的营养和能量需求。此外，在动物模型中，自噬可以预防疾病，如癌症，神经退行性疾病，感染，炎症性疾病，衰老和胰岛素抵抗。在这里，我们表明急性运动会诱导进食小鼠骨骼肌和心肌的自噬。为了研究运动介导的自噬在体内的作用，我们产生了突变小鼠，这些小鼠显示出正常水平的基础自噬，但缺乏刺激（运动或饥饿）诱导的自噬。这些小鼠（称为BCL 2 AAA小鼠）在BCL 2磷酸化位点（Thr 69 Ala、Ser 70 Ala和Ser 84 Ala）中含有敲入突变，其防止刺激诱导的BCL 2-beclin-1复合物的破坏和自噬激活。BCL 2 AAA小鼠在急性运动期间表现出耐力下降和葡萄糖代谢改变，以及慢性运动介导的对高脂饮食诱导的葡萄糖耐受不良的保护受损。因此，运动诱导自噬，BCL 2是体内运动（和饥饿）诱导的自噬的关键调节因子，自噬诱导可能有助于运动的有益代谢作用。
Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes. However, the cellular mechanisms underlying these effects are incompletely understood. The lysosomal degradation pathway, autophagy, is an intracellular recycling system that functions during basal conditions in organelle and protein quality control. During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism. Moreover, in animal models, autophagy protects against diseases such as cancer, neuro-degenerative disorders, infections, inflammatory diseases, ageing and insulin resistance. Here we show that acute exercise induces autophagy in skeletal and cardiac muscle of fed mice. To investigate the role of exercise-mediated autophagy in vivo, we generated mutant mice that show normal levels of basal autophagy but are deficient in stimulus (exercise- or starvation)-induced autophagy. These mice (termed BCL2 AAA mice) contain knock-in mutations in BCL2 phosphorylation sites (Thr69Ala, Ser70Ala and Ser84Ala) that prevent stimulus-induced disruption of the BCL2-beclin-1 complex and autophagy activation. BCL2 AAA mice show decreased endurance and altered glucose metabolism during acute exercise, as well as impaired chronic exercise-mediated protection against high-fat-diet-induced glucose intolerance. Thus, exercise induces autophagy, BCL2 is a crucial regulator of exercise- (and starvation)- induced autophagy in vivo, and autophagy induction may contribute to the beneficial metabolic effects of exercise.
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运动和PGC1alpha在炎症和慢性疾病中的作用。
影响因子：
64.8
作者：
Handschin, Christoph;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
DOI：
10.1073/pnas.1332160100
发表时间：
2003-06-24
影响因子：
11.1
作者：
Su, T;Suzui, M;Weinstein, IB
通讯作者：
Weinstein, IB
影响因子：
13.3
作者：
Furuya, Norihiko;Yu, Jie;Levine, Beth
通讯作者：
Levine, Beth
影响因子：
29
作者：
Ebato, Chie;Uchida, Toyoyoshi;Watada, Hirotaka
通讯作者：
Watada, Hirotaka
影响因子：
3.3
作者：
Mizushima, N;Yamamoto, A;Ohsumi, Y
通讯作者：
Ohsumi, Y