High-fat diet induces mouse liver steatosis with a concomitant decline in energy metabolism: attenuation by eicosapentaenoic acid (EPA) or hydroxytyrosol (HT) supplementation and the additive effects upon EPA and HT co-administration
High-fat diet induces mouse liver steatosis with a concomitant decline in energy metabolism: attenuation by eicosapentaenoic acid (EPA) or hydroxytyrosol (HT) supplementation and the additive effects upon EPA and HT co-administration
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DOI：
10.1039/c9fo01373c
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发表时间：
2019-09-01
期刊：
影响因子：
6.1
通讯作者：
Videla, Luis A.
中科院分区：
文献类型：
--
作者：
Echeverria, Francisca;Valenzuela, Rodrigo;Videla, Luis A.
高脂饮食（HFD）喂养与肝脏氧化应激（OS）、n-3长链多不饱和脂肪酸（n-3 LCPUFA）耗竭、肝脏脂肪变性和线粒体功能障碍相关。我们的假设是，HFD诱导的肝损伤可以通过联合补充n-3 LCPUFA二十碳五烯酸（EPA）和抗氧化剂羟基酪醇（HT）来减轻。向C57 BL/6 J小鼠施用HFD（60%脂肪，20%蛋白质，20%碳水化合物）或对照饮食（CD; 10%脂肪，20%蛋白质，70%碳水化合物），含或不含EPA（50 mg kg（-1）天（-1）），HT（5 mg kg（-1）天（-1）），或EPA + HT（分别为50和5 mg kg（-1）天（-1）），持续12周。我们测量了体重和肝脏重量以及饮食和能量摄入沿着，以及肝脏组织学、FA组成、脂肪变性评分和相关转录因子、线粒体功能以及通过AMP活化蛋白激酶（AMPK）和PPAR-gamma共激活因子-1 α（PGC-1 α）级联与能量感知相关的代谢因子。发现HFD显著诱导肝脏脂肪变性，与CD的情况相比，n-3 LCPUFA消耗66%，n-6/n-3 LCPUFA比率增加100%（p < 0.05）。这些变化伴随着（i）95%的脂肪生成和70%的FA氧化信号降低，（ii）线粒体呼吸能力降低40%和（iii）ATP含量降低56%。HFD诱导的肝脏脂肪变性还与（iv）AMPK-PGC-1 α信号传导组分、核呼吸因子-2（NRF-2）和β-ATP合酶的mRNA表达降低相关。这些HFD效应通过EPA + HT的组合补充以累加方式显著减弱。这些结果表明，EPA和HT联合给药部分预防了HFD诱导的肝脏脂肪变性，从而加强了联合干预在非酒精性脂肪性肝病肝脏保护中的重要性。
High-fat-diet (HFD) feeding is associated with liver oxidative stress (OS), n-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA) depletion, hepatic steatosis and mitochondrial dysfunction. Our hypothesis is that the HFD-induced liver injury can be attenuated by the combined supplementation of n-3 LCPUFA eicosapentaenoic acid (EPA) and the antioxidant hydroxytyrosol (HT). The C57BL/6J mice were administered an HFD (60% fat, 20% protein, 20% carbohydrates) or control diet (CD; 10% fat, 20% protein, 70% carbohydrates), with or without EPA (50 mg kg(-1) day(-1)), HT (5 mg kg(-1) day(-1)), or EPA + HT (50 and 5 mg kg(-1) day(-1), respectively) for 12 weeks. We measured the body and liver weights and dietary and energy intakes along with liver histology, FA composition, steatosis score and associated transcription factors, mitochondrial functions and metabolic factors related to energy sensing through the AMP-activated protein kinase (AMPK) and PPAR-gamma coactivator-1 alpha (PGC-1 alpha) cascade. It was found that the HFD significantly induced liver steatosis, with a 66% depletion of n-3 LCPUFAs and a 100% increase in n-6/n-3 LCPUFA ratio as compared to the case of CD (p < 0.05). These changes were concomitant with (i) a 95% higher lipogenic and 70% lower FA oxidation signaling, (ii) a 40% diminution in mitochondrial respiratory capacity and (iii) a 56% lower ATP content. HFD-induced liver steatosis was also associated with (iv) a depressed mRNA expression of AMPK-PGC-1 alpha signaling components, nuclear respiratory factor-2 (NRF-2) and beta-ATP synthase. These HFD effects were significantly attenuated by the combined EPA + HT supplementation in an additive manner. These results suggested that EPA and HT co-administration partly prevented HFD-induced liver steatosis, thus strengthening the importance of combined interventions in hepatoprotection in non-alcoholic fatty liver disease.