Department of Cellular and Molecular Physiology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA; email:
Annu Rev Nutr. 2018 Aug 21;38:197-217. doi: 10.1146/annurev-nutr-071816-064642.
Both acute intoxication and longer-term cumulative ingestion of alcohol negatively impact the metabolic phenotype of both skeletal and cardiac muscle, independent of overt protein calorie malnutrition, resulting in loss of skeletal muscle strength and cardiac contractility. In large part, these alcohol-induced changes are mediated by a decrease in protein synthesis that in turn is governed by impaired activity of a protein kinase, the mechanistic target of rapamycin (mTOR). Herein, we summarize recent advances in understanding mTOR signal transduction, similarities and differences between the effects of alcohol on this central metabolic controller in skeletal muscle and in the heart, and the effects of acute versus chronic alcohol intake. While alcohol-induced alterations in global proteolysis via activation of the ubiquitin-proteasome pathway are equivocal, emerging data suggest alcohol increases autophagy in muscle. Further studies are necessary to define the relative contributions of these bidirectional changes in protein synthesis and autophagy in the etiology of alcoholic myopathy in skeletal muscle and the heart.
急性中毒和长期累积摄入酒精会对骨骼肌和心肌的代谢表型产生负面影响，而不论是否存在明显的蛋白质-热量营养不良，导致骨骼肌力量丧失和心脏收缩力下降。在很大程度上，这些酒精引起的变化是通过蛋白质合成减少介导的，而蛋白质合成减少又受到蛋白激酶活性的影响，即雷帕霉素靶蛋白（mTOR）。本文总结了近年来对 mTOR 信号转导的理解进展，酒精对骨骼肌和心脏中这一核心代谢控制器的影响的异同，以及急性和慢性酒精摄入的影响。虽然通过激活泛素-蛋白酶体途径导致的整体蛋白水解的酒精诱导改变尚存在争议，但新出现的数据表明酒精会增加肌肉中的自噬。需要进一步的研究来确定蛋白质合成和自噬这两个相互作用的变化在骨骼肌和心脏中酒精性肌病发病机制中的相对贡献。
