Mitochondria in nonalcoholic fatty liver disease.
Mitochondria in nonalcoholic fatty liver disease.
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DOI：
10.1016/j.cld.2004.04.009
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发表时间：
2004-08-01
影响因子：
5.1
通讯作者：
Krugner-Higby, Lisa
中科院分区：
文献类型：
--
作者：
Caldwell, Stephen H;Chang, Charissa Y;Krugner-Higby, Lisa
非酒精性脂肪肝（NAFL）与脂肪代谢和胰岛素抵抗的基本问题有关。这些异常与ATP稳态受损有关，越来越多的文献报道了各种形式的肝脂肪变性中的线粒体异常。这些变化是明显的结构异常，包括大大增加的大小和结晶夹杂物的发展，通常被认为是病理性的，反映了对损伤的保护性或退行性反应。尽管结构变化、线粒体功能下降和疾病状态之间的关系越来越清楚，但对这些扰动的分子基础还没有很好的理解。氧化损伤是最有可能的致病过程，并可能导致线粒体DNA（mtDNA）的改变，刺激凋亡途径，增加坏死倾向。整体线粒体健康可能取决于多种因素，包括mtDNA的完整性，细胞脂质的组成，脂蛋白运输，前和抗氧化因子的平衡，以及对肝脏的代谢需求。线粒体功能障碍可能在与NAFL相关的许多临床病症中起作用，例如肝细胞癌、脂肪营养不良、年龄相关的胰岛素抵抗、肠道动力障碍、隐源性肝硬化、轻度形式的凝视麻痹以及可能的其他更严重的神经退行性疾病。线粒体功能障碍在NAFL中的突出作用提供了一个新的和令人兴奋的范例，以查看这种疾病，其并发症，以及潜在的饮食和药物干预。
Nonalcoholic fatty liver (NAFL) is associated with fundamental issues of fat metabolism and insulin resistance. These abnormalities have been linked to impairment of ATP homeostasis, and a growing body of literature has reported mitochondrial abnormalities in various forms of hepatic steatosis. The changes are evident as structural abnormalities, including greatly increased size and the development of crystalline inclusions, and are usually regarded as pathologic, reflecting either a protective or degenerative response to injury. Although the relationships between structural changes,decreased mitochondrial function, and disease states are becoming clearer, the molecular basis for the perturbations is not well understood. Oxidative damage is the most likely causative process and may result in alterations of mitochondrial DNA (mtDNA), stimulated apoptotic pathways, and increased propensity for necrosis.Overall mitochondrial health likely depends on multiple factors including the integrity of the mtDNA, the composition of cellular lipids, lipoprotein trafficking, the balance of pro- and antioxidant factors, and the metabolic demands placed on the liver. Mitochondrial dysfunction may play a role in numerous clinical conditions associated with NAFL, such as hepatocellular carcinoma, lipodystrophy,age-related insulin resistance, gut dysmotility, cryptogenic cirrhosis, a mild form of gaze palsy, and possibly other more severe neurodegenerative diseases. The prominent role of mitochondrial dysfunction in NAFL provides a new and exciting paradigm in which to view this disorder, its complications, and potential dietary and pharmacologic intervention.