(-)-Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy.
(-)-Epicatechin induces mitochondrial biogenesis and markers of muscle regeneration in adults with Becker muscular dystrophy.
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DOI：
10.1002/mus.27108
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发表时间：
2021-03
期刊：
影响因子：
3.4
通讯作者：
Henricson EK
中科院分区：
文献类型：
--
作者：
McDonald CM;Ramirez-Sanchez I;Oskarsson B;Joyce N;Aguilar C;Nicorici A;Dayan J;Goude E;Abresch RT;Villarreal F;Ceballos G;Perkins G;Dugar S;Schreiner G;Henricson EK
我们进行了一项开放标签研究，以检查类黄酮（-）-表儿茶素在7名患有贝克尔肌营养不良症（BMD）的非卧床成人患者中的作用。7名参与者接受（-）-表儿茶素50 mg，每天两次，持续8周。手术前和手术后包括肱二头肌活检，通过蛋白质印迹法评估肌肉结构和生长相关终点、线粒体体积测量、电子显微镜下的嵴丰度、分级运动测试以及肌肉力量和功能测试。蛋白质印迹法显示调节细胞生物能量学的酶（肝激酶B1和5′-腺苷一磷酸活化蛋白激酶）水平显著增加。过氧化物酶体增殖物激活受体γ辅激活因子-1 α，一种参与线粒体生物发生和嵴相关丝裂素水平的基因转录辅激活因子，随着嵴丰度的增加而增加。肌肉和血浆卵泡抑素显著增加，而肌肉生长抑制素减少。骨骼肌再生肌生成素、肌生成调节因子-5、成肌细胞决定蛋白1、肌细胞增强因子-2和结构相关蛋白（包括dysferlin、utrophin和细胞内肌酸激酶）的标志物也增加。运动试验表明，在规定的工作负荷下，心率、每公斤最大耗氧量和血浆乳酸水平降低。组织饱和指数在休息和运动后状态改善。（−）-表儿茶素是一种运动模拟物，似乎对指示线粒体生物发生和肌肉再生的组织生物标志物具有短期积极作用，并改善了BMD患者的分级运动测试参数。
We conducted an open‐label study to examine the effects of the flavonoid (−)‐epicatechin in seven ambulatory adult patients with Becker muscular dystrophy (BMD). Seven participants received (−)‐epicatechin 50 mg twice per day for 8 weeks. Pre‐ and postprocedures included biceps brachii biopsy to assess muscle structure and growth‐relevant endpoints by western blotting, mitochondria volume measurement, and cristae abundance by electron microscopy, graded exercise testing, and muscle strength and function tests. Western blotting showed significantly increased levels of enzymes modulating cellular bioenergetics (liver kinase B1 and 5′‐adenosine monophosphate–activated protein kinase). Peroxisome proliferator‐activated receptor gamma coactivator‐1alpha, a transcriptional coactivator of genes involved in mitochondrial biogenesis and cristae‐associated mitofilin levels, increased as did cristae abundance. Muscle and plasma follistatin increased significantly while myostatin decreased. Markers of skeletal muscle regeneration myogenin, myogenic regulatory factor‐5, myoblast determination protein 1, myocyte enhancer factor‐2, and structure‐associated proteins, including dysferlin, utrophin, and intracellular creatine kinase, also increased. Exercise testing demonstrated decreased heart rate, maximal oxygen consumption per kilogram, and plasma lactate levels at defined workloads. Tissue saturation index improved in resting and postexercise states. (−)‐Epicatechin, an exercise mimetic, appears to have short‐term positive effects on tissue biomarkers indicative of mitochondrial biogenesis and muscle regeneration, and produced improvements in graded exercise testing parameters in patients with BMD.
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影响因子：
64.8
作者：
Handschin, Christoph;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
64.8
作者：
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Puigserver, P
DOI：
10.1073/pnas.0705070104
发表时间：
2007-07-17
影响因子：
11.1
作者：
Jaeger, Sibylle;Handschin, Christoph;Spiegelman, Bruce M.
通讯作者：
Spiegelman, Bruce M.
影响因子：
3.4
作者：
Gordon, Bradley S.;Lowe, Dawn A.;Kostek, Matthew C.
通讯作者：
Kostek, Matthew C.
影响因子：
7.3
作者：
Hernández-Hernández JM;García-González EG;Brun CE;Rudnicki MA
通讯作者：
Rudnicki MA