Attenuation of High-Fat Diet-Induced Rat Liver Oxidative Stress and Steatosis by Combined Hydroxytyrosol- (HT-) Eicosapentaenoic Acid Supplementation Mainly Relies on HT.

Attenuation of High-Fat Diet-Induced Rat Liver Oxidative Stress and Steatosis by Combined Hydroxytyrosol- (HT-) Eicosapentaenoic Acid Supplementation Mainly Relies on HT.
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DOI:
10.1155/2018/5109503
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发表时间:
2018
影响因子:
--
通讯作者:
Videla LA
Videla LA
中科院分区:
生物学2区
文献类型:
--
作者:
Echeverría F;Valenzuela R;Bustamante A;Álvarez D;Ortiz M;Soto-Alarcon SA;Muñoz P;Corbari A;Videla LA

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非酒精性脂肪性肝病(NAFLD)的药物治疗目前尚未获批。为此,本研究评估了二碳五烯酸(EPA, 50 mg/kg/天)调节肝脏脂质代谢和羟基酪醇(HT, 5 mg/kg/天)对高脂饮食(HFD, 60%脂肪,20%蛋白质和20%碳水化合物)与对照饮食(CD, 10%脂肪,20%蛋白质和70%碳水化合物)诱导的小鼠肝脏脂肪变性和氧化应激的影响。HFD诱导的肝脂肪变性(i)由EPA减少32%,氧化应激相关参数不变,Nrf2功能轻度恢复,提供抗氧化作用;(ii)由HT减少42%,同时HFD减少的谷胱甘肽状态总恢复,HFD增强的脂质过氧化和蛋白质氧化恢复42%至59%,Nrf2功能恢复,而(iii) EPA + HT联合补充可使肝脏脂肪变性减少74%。总抗氧化潜能恢复的方式与高温疗法相似。由此可见,HT + EPA联用可显著降低NAFLD的发展,其作用表现为HT与EPA作用的加和性,而HT的作用主要依赖于EPA,强化了氧化应激的影响,是肥胖肝脂肪变性的核心机制。
Pharmacological therapy for nonalcoholic fatty liver disease (NAFLD) is not approved at the present time. For this purpose, the effect of combined eicosapentaenoic acid (EPA; 50 mg/kg/day) modulating hepatic lipid metabolism and hydroxytyrosol (HT; 5 mg/kg/day) exerting antioxidant actions was evaluated on hepatic steatosis and oxidative stress induced by a high-fat diet (HFD; 60% fat, 20% protein, and 20% carbohydrates) compared to a control diet (CD; 10% fat, 20% protein, and 70% carbohydrates) in mice fed for 12 weeks. HFD-induced liver steatosis (i) was reduced by 32% by EPA, without changes in oxidative stress-related parameters and mild recovery of Nrf2 functioning affording antioxidation and (ii) was decreased by 42% by HT, concomitantly with total regain of the glutathione status diminished by HFD, 42% to 59% recovery of lipid peroxidation and protein oxidation enhanced by HFD, and regain of Nrf2 functioning, whereas (iii) combined EPA + HT supplementation elicited 74% reduction in liver steatosis, with total recovery of the antioxidant potential in a similar manner than HT. It is concluded that combined HT + EPA drastically decreases NAFLD development, an effect that shows additivity in HT and EPA effects that mainly relies on HT, strengthening the impact of oxidative stress as a central mechanism underlying liver steatosis in obesity.
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