Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: Effect of the nutritional status
Mitochondrial oxidative injury and energy metabolism alteration in rat fatty liver: Effect of the nutritional status
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DOI：
10.1053/jhep.2001.23060
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发表时间：
2001-04-01
期刊：
影响因子：
13.5
通讯作者：
Altomare, E
中科院分区：
文献类型：
--
作者：
Vendemiale, G;Grattagliano, I;Altomare, E
肝脂肪变性与线粒体氧化改变有关。本研究的目的是在胆碱缺乏模型的大鼠脂肪肝的特点是否这种氧化失衡与ATP合成能力的损害，无论是在进食条件下，饥饿后，这可能会敏感的线粒体氧化损伤。线粒体分离自正常和脂肪肝的喂养或禁食18小时的大鼠。氧化损伤通过测量硫代巴比妥反应物质、蛋白质羰基、谷胱甘肽和蛋白质巯基的线粒体含量来评估。与正常肝相比，脂肪肝在进食状态下线粒体氧化脂质和蛋白质含量增加，巯基和谷胱甘肽含量降低。在脂肪肝中，线粒体催化F0 F1-ATP合酶的β-F-1亚基降低了约35%。在脂肪肝中，肝ATP也显著降低。饥饿加剧了两组的线粒体氧化损伤，但在更大程度上脂肪肝。在脂肪变性组中，禁食导致ATP水平显著降低，伴随着催化β-F-1亚单位下降70%。这些数据表明，脂肪肝中的线粒体氧化改变与F0 F1-ATP合酶的重要减少有关。这些变化在饥饿后大大加剧，可能是脂肪浸润存在下观察到的肝ATP合成减少的原因。
Hepatic steatosis is associated with mitochondrial oxidative alterations. This study aimed to characterize in a choline-deficient model of rat fatty liver whether this oxidative imbalance is related to an impairment of the capacity of ATP synthesis both under fed conditions and after starvation, which may sensitize mitochondria to oxidative injury. Mitochondria were isolated from normal and fatty livers of fed or 18-hour fasted rats. Oxidative injury was evaluated by measuring the mitochondrial content of thiobarbituric reactive substances, protein carbonyls, glutathione, and protein sulfhydryls. The mitochondrial F0F1-ATP synthase content, tissue ATP concentration, and fiver histology were also determined, Compared with normal liver, under fed conditions, fatty livers showed a greater mitochondrial content of oxidized lipids and proteins together with a low concentration of sulfhydryls and glutathione. The mitochondrial catalytic beta -F-1 subunit of the F0F1-ATP synthase was about 35% lower in fatty livers. Hepatic ATP was also significantly reduced in fatty liver. Starvation exacerbated mitochondrial oxidative injury in both groups but to a greater extent in fatty livers. in the steatotic group, fasting induced a significant decrease of the ATP levels, which was accompanied by a 70% fall of the catalytic beta -F-1 subunit. These data indicate that the mitochondrial oxidative alterations in fatty livers are associated with an important reduction of the F0F1-ATP synthase, These changes, which are greatly exacerbated after starvation, may account for the reduced synthesis of the hepatic ATP observed in the presence of fatty infiltration.