Nonalcoholic fatty liver disease (NAFLD) is the leading liver chronic disease featuring hepatic steatosis. Mitochondrial β-oxidation participates in the derangement of lipid metabolism at the basis of NAFLD, and mitochondrial oxidative stress contributes to the onset of the disease. We evaluated the presence and effects of mitochondrial oxidative stress in the liver from rats fed a high-fat plus fructose (HF-F) diet inducing NAFLD. Supplementation with dehydroepiandrosterone (DHEA), a multitarget antioxidant, was tested for efficacy in delaying NAFLD. A marked mitochondrial oxidative stress was originated by all diets, as demonstrated by the decrease in Superoxide Dismutase 2 (SOD2) and Peroxiredoxin III (PrxIII) amounts. All diets induced a decrease in mitochondrial DNA content and an increase in its oxidative damage. The diets negatively affected mitochondrial biogenesis as shown by decreased peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α), mitochondrial transcription factor A (TFAM), and the COX-IV subunit from the cytochrome c oxidase complex. The reduced amounts of Beclin-1 and lipidated LC3 II form of the microtubule-associated protein 1 light chain 3 (LC3) unveiled the diet-related autophagy’s decrease. The DHEA supplementation did not prevent the diet-induced changes. These results demonstrate the relevance of mitochondrial oxidative stress and the sequential dysfunction of the organelles in an obesogenic diet animal model of NAFLD.

中文翻译：

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非酒精性脂肪肝动物模型中的线粒体触发因素


非酒精性脂肪肝病（NAFLD）是主要的以肝脂肪变性为特征的肝脏慢性疾病。线粒体β-氧化参与了NAFLD基础上的脂质代谢紊乱，线粒体氧化应激导致了该病的发生。我们评估了喂食高脂加果糖（HF-F）饮食诱导 NAFLD 的大鼠肝脏中线粒体氧化应激的存在及其影响。测试了补充脱氢表雄酮 (DHEA)（一种多靶点抗氧化剂）延缓 NAFLD 的功效。所有饮食都会产生显着的线粒体氧化应激，超氧化物歧化酶 2 (SOD2) 和过氧化还原蛋白 III (PrxIII) 含量的减少就证明了这一点。所有饮食都会导致线粒体 DNA 含量减少和氧化损伤增加。饮食对线粒体生物发生产生负面影响，具体表现为过氧化物酶体增殖物激活受体-γ 共激活剂-1α (PGC-1α)、线粒体转录因子 A (TFAM) 和细胞色素 c 氧化酶复合物中的 COX-IV 亚基的减少。 Beclin-1 和微管相关蛋白 1 轻链 3 (LC3) 脂化 LC3 II 形式的减少揭示了与饮食相关的自噬的减少。补充 DHEA 并不能阻止饮食引起的变化。这些结果证明了 NAFLD 肥胖饮食动物模型中线粒体氧化应激与细胞器连续功能障碍的相关性。