Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation
Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation
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DOI：
10.1080/17461391.2019.1571114
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发表时间：
2019-08-09
影响因子：
3.2
通讯作者：
Azarbayjani, Mohammad Ali
中科院分区：
文献类型：
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作者：
Farzanegi, Parvin;Dana, Amir;Azarbayjani, Mohammad Ali
非酒精性脂肪性肝病（NAFLD）是一种常见的慢性肝病，与肝脏中的脂肪积累有关。它会引起各种各样的病理效应，如非酒精性脂肪性肝炎（NASH）和肝硬化、胰岛素抵抗、肥胖、高血压、血脂异常、糖尿病和心血管疾病。导致NAFLD发生和发展的分子机制尚未完全了解。活性氧（reactive oxygen species，ROS）和炎症反应诱导的氧化应激（Oxidative stress，OS）可能是导致肝细胞死亡和组织损伤的重要机制。线粒体异常、几种抗氧化酶的下调、谷胱甘肽（GSH）耗竭和GSH依赖性抗氧化剂活性降低、白细胞积聚和肝脏炎症是NAFLD中ROS过度产生的主要来源。ROS的过度产生抑制了NAFLD中其他抗氧化防御系统的能力，并导致进一步的氧化损伤。定期运动可以被认为是治疗NAFLD的有效策略。它通过减少肝内脂肪含量、增加脂肪酸的β-氧化、诱导肝保护性自噬、过表达过氧化物酶体增殖物激活受体-γ（PPAR-gamma）以及减弱肝细胞凋亡和增加胰岛素敏感性来改善NAFLD。运动训练还通过上调几种抗氧化酶和抗炎介质来抑制NAFLD中ROS的过度产生和OS。因此，对这些分子和信号通路的理解为我们提供了关于NAFLD进展的有价值的信息，以及开发合适的临床治疗方法的方法。本文综述了NAFLD中ROS和OS的来源以及运动对NAFLD有益作用的分子机制。
Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disorder which is associated with accumulation of fats in the liver. It causes a wide variety of pathological effects such as non-alcoholic steatohepatitis (NASH) and cirrhosis, insulin resistance, obesity, hypertension, dyslipidaemia, diabetes and cardiovascular disease. The molecular mechanisms that cause the initiation and progression of NAFLD are not fully understood. Oxidative stress (OS) induced by reactive oxygen species (ROS) and inflammation are likely a significant mechanism which can lead to hepatic cell death and tissue injury. Mitochondrial abnormalities, down-regulation of several antioxidant enzymes, glutathione (GSH) depletion and decreased activity of GSH-dependent antioxidants, accumulation of leukocytes and hepatic inflammation are the major sources of ROS overproduction in NAFLD. Excessive production of ROS suppresses the capacity of other antioxidant defence systems in NAFLD and causes further oxidative damage. Regular exercise can be considered as an effective strategy for treatment of NAFLD. It improves NAFLD by reducing intrahepatic fat content, increasing beta-oxidation of fatty acids, inducing hepato-protective autophagy, overexpressing peroxisome proliferator-activated receptor- gamma (PPAR-gamma), as well as attenuating hepatocyte apoptosis and increasing insulin sensitivity. Exercise training also suppresses ROS overproduction and OS in NAFLD via up-regulation of several antioxidant enzymes and anti-inflammatory mediators. Therefore, an understanding of these molecules and signalling pathways gives us valuable information about NAFLD progression and a method for developing a suitable clinical treatment. This review aimed to evaluate sources of ROS and OS in NAFLD and the molecular mechanisms involved in the beneficial effects of exercises on NAFLD.