The severity of rat liver injury by fructose and high fat depends on the degree of respiratory dysfunction and oxidative stress induced in mitochondria
The severity of rat liver injury by fructose and high fat depends on the degree of respiratory dysfunction and oxidative stress induced in mitochondria
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DOI：
10.1186/s12944-019-1024-5
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发表时间：
2019-03-30
影响因子：
4.5
通讯作者：
Cortes-Rojo, Christian
中科院分区：
文献类型：
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作者：
Isabel Garcia-Berumen, Claudia;Ortiz-Avila, Omar;Cortes-Rojo, Christian
背景：高脂肪或果糖诱导非酒精性脂肪性肝病（NAFLD）伴线粒体功能障碍和氧化应激。关于果糖还是脂肪对NAFLD的发展更有害的争论仍然存在。为了更深入地了解这一问题，并确定果糖或脂肪引起的肝脏疾病的严重程度是否与线粒体功能障碍的程度有关，我们比较了含有高脂肪（HF）、果糖（Fr）或高脂肪加果糖（HF+Fr）的饮食对NAFLD发展、线粒体功能、ROS产生和脂质过氧化的影响。方法将swistar大鼠分为4组：对照组，饲喂标准鼠粮；高脂肪（HF），添加猪油和氢化植物油；果糖（Fr），在饮用水中添加25%的果糖；高脂肪加果糖组（HF+Fr），饲喂HF和Fr两种饲粮。喂养6周后处死大鼠，切除肝脏进行苏木精、伊红染色和线粒体分离的组织病理学分析。通过测量线粒体呼吸和复合体I活性来评估线粒体功能。采用硫代巴比妥酸法和荧光ROS探针2,4- h (2)DCFDA分别评价线粒体的脂质过氧化和ROS生成。结果fr组大鼠肝脏损伤程度较低，线粒体功能障碍程度较低，肝细胞微泡性脂肪变性比例低于20%，3态呼吸功能部分降低。HF组表现出中等程度的损伤，40%的肝细胞出现微泡性脂肪变性，状态3呼吸和复合体I活性均降低。HF+Fr组表现出更严重的损伤，60%的肝细胞出现微泡性脂肪变性和炎症，而线粒体表现出完全抑制状态3呼吸，复合物I活性受损，ROS生成增加。Fr组和HF+Fr组均观察到线粒体脂质过氧化加剧。结论果糖或脂肪所致肝损伤的严重程度与线粒体功能障碍程度和氧化损伤程度有关。应注意hf +Fr组观察到的严重影响，因为典型的西方饮食富含脂肪和碳水化合物。
BackgroundHigh fat or fructose induces non-alcoholic fatty liver disease (NAFLD) accompanied of mitochondrial dysfunction and oxidative stress. Controversy remains about whether fructose or fat is more deleterious for NAFLD development. To get more insights about this issue and to determine if the severity of liver disease induced by fructose or fat is related to degree of mitochondrial dysfunction, we compared the effects of diets containing high fat (HF), fructose (Fr) or high fat plus fructose (HF+Fr) on NAFLD development, mitochondrial function, ROS production and lipid peroxidation.MethodsWistar rats were assigned to four groups: Control, fed with standard rodent chow; High fat (HF), supplemented with lard and hydrogenated vegetable oil; Fructose (Fr), supplemented with 25% fructose in the drinking water; High fat plus fructose group (HF+Fr), fed with both HF and Fr diets. Rats were sacrificed after 6 weeks of diets consumption and the liver was excised for histopathological analysis by hematoxylin and eosin staining and for mitochondria isolation. Mitochondrial function was evaluated by measuring both mitochondrial respiration and complex I activity. Lipid peroxidation and ROS production were evaluated in mitochondria by the thiobarbituric acid method and with the fluorescent ROS probe 2,4-H(2)DCFDA, respectively.ResultsFr group underwent the lower degree of both liver damage and mitochondrial dysfunction that manifested like less than 20% of hepatocytes with microvesicular steatosis and partial decrease in state 3 respiration, respectively. HF group displayed an intermediate degree of damage as it showed 40% of hepatocytes with microvesicular steatosis and diminution of both state 3 respiration and complex I activity. HF+Fr group displayed more severe damage as showed microvesicular steatosis in 60% of hepatocytes and inflammation, while mitochondria exhibited fully inhibited state 3 respiration, impaired complex I activity and increased ROS generation. Exacerbation of mitochondrial lipid peroxidation was observed in both the Fr and HF+Fr groups.ConclusionSeverity of liver injury induced by fructose or fat was related to the degree of dysfunction and oxidative damage in mitochondria. Attention should be paid on the serious effects observed in theHF+Fr group as the typical Western diet is rich in both fat and carbohydrates.