Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats
Long-term intake of a high-protein diet increases liver triacylglycerol deposition pathways and hepatic signs of injury in rats
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DOI：
10.1016/j.jnutbio.2017.04.008
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发表时间：
2017-08-01
影响因子：
5.6
通讯作者：
Oliver, Paula
中科院分区：
文献类型：
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作者：
Diaz-Rua, Ruben;Keijer, Jaap;Oliver, Paula
高蛋白(HP)饮食的摄入量在过去几年里有所增加，主要是因为它们在控制体重方面很受欢迎。肝脏是处理摄入的常量营养素的主要器官，它与不同病理的开始有关。我们的目标是加深我们对长期摄入HP饮食影响的分子通路的了解。我们对长期饲喂富含酪蛋白的HP饮食的大鼠的肝脏进行了转录组分析，并分析了与肝损伤相关的分子参数。饮食中蛋白质/碳水化合物比例的慢性增加上调了与氨基酸吸收/代谢和脂肪合成相关的过程，促进了表明肝脏三酰甘油(TG)沉积的分子环境。此外，涉及酸碱维持和氧化应激的基因表达的变化表明，由于饮食的高酸负荷，pH平衡发生了变化，这与肝脏/健康损害有关。免疫相关基因的上调也被观察到。与基因表达水平的变化相一致，我们观察到肝脏甘油三酯含量增加，血清肝损伤/炎症标志物(天冬氨酸转氨酶、C反应蛋白和肿瘤坏死因子-α)增加。此外，HP饮食显著增加了肝脏HSP90的mRNA和蛋白水平，HSP90是肝脏损伤的标志。因此，我们首次表明，长期食用HP饮食，导致高酸负荷，导致肝脏转录组特征，反映TG沉积增加和健康风险增加的迹象(炎症增加，酸碱平衡和氧化应激改变)。这种代谢状态的持续变化可能会产生不健康的后果。(C)2017 Elsevier Inc.保留所有权利。
Intake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition. Moreover, changes in expression of genes involved in acid-base maintenance and oxidative stress indicate alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. Up-regulation of immune-related genes was also observed. In concordance with changes at gene expression level, we observed increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly increased hepatic mRNA and protein levels of HSP90, a marker of liver injury. Thus, we show for the first time that long-term consumption of an HP diet, resulting in a high acid load, results in a hepatic transcriptome signature reflecting increased TG deposition and increased signs of health risk (increased inflammation, alterations in the acid-base equilibrium and oxidative stress). Persistence of this altered metabolic status could have unhealthy consequences. (C) 2017 Elsevier Inc. All rights reserved.