Importance of Serum Amino Acid Profile for Induction of Hepatic Steatosis under Protein Malnutrition.
Importance of Serum Amino Acid Profile for Induction of Hepatic Steatosis under Protein Malnutrition.
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DOI：
10.1038/s41598-018-23640-8
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发表时间：
2018-04-03
影响因子：
4.6
通讯作者：
Takahashi SI
中科院分区：
文献类型：
--
作者：
Nishi H;Yamanaka D;Kamei H;Goda Y;Kumano M;Toyoshima Y;Takenaka A;Masuda M;Nakabayashi Y;Shioya R;Kataoka N;Hakuno F;Takahashi SI
我们以前报道过，低蛋白饮食会导致动物产生含有高水平甘油三酯（TG）的脂肪肝，类似于人类营养失调症“恶性营养不良症”。为了研究潜在的机制，我们在氨基酸充足或缺乏的培养基中培养肝细胞。令人惊讶的是，细胞内TG水平增加氨基酸缺乏，而不添加任何脂质或激素，伴随着增强的脂质合成，这表明肝细胞本身监测细胞外氨基酸浓度，以细胞自主的方式诱导脂质积累。我们随后证实，低氨基酸饮食也导致脂肪肝的发展，并且补充低氨基酸饮食中的谷氨酸以补偿氮源的损失并不能完全抑制肝脏TG的积累。只有饮食精氨酸或苏氨酸缺乏足以诱导肝脏TG积累。然而，补充精氨酸或苏氨酸的低氨基酸饮食未能扭转it.In silico分析成功地预测肝脏TG水平从血清氨基酸谱。基于这些结果，我们得出结论，膳食氨基酸组成动态影响血清氨基酸谱，这是由肝细胞和脂质合成被激活细胞自主，导致肝脂肪变性。
We previously reported that a low-protein diet caused animals to develop fatty liver containing a high level of triglycerides (TG), similar to the human nutritional disorder “kwashiorkor”. To investigate the underlying mechanisms, we cultured hepatocytes in amino acid-sufficient or deficient medium. Surprisingly, the intracellular TG level was increased by amino acid deficiency without addition of any lipids or hormones, accompanied by enhanced lipid synthesis, indicating that hepatocytes themselves monitored the extracellular amino acid concentrations to induce lipid accumulation in a cell-autonomous manner. We then confirmed that a low-amino acid diet also resulted in the development of fatty liver, and supplementation of the low-amino acid diet with glutamic acid to compensate the loss of nitrogen source did not completely suppress the hepatic TG accumulation. Only a dietary arginine or threonine deficiency was sufficient to induce hepatic TG accumulation. However, supplementation of a low-amino acid diet with arginine or threonine failed to reverse it. In silico analysis succeeded in predicting liver TG level from the serum amino acid profile. Based on these results, we conclude that dietary amino acid composition dynamically affects the serum amino acid profile, which is sensed by hepatocytes and lipid synthesis was activated cell-autonomously, leading to hepatic steatosis.
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影响因子：
64.8
作者：
RUMELHART, DE;HINTON, GE;WILLIAMS, RJ
通讯作者：
WILLIAMS, RJ
影响因子：
64.5
作者：
Chantranupong L;Scaria SM;Saxton RA;Gygi MP;Shen K;Wyant GA;Wang T;Harper JW;Gygi SP;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
1.9
作者：
KOHONEN, T
通讯作者：
KOHONEN, T
影响因子：
4.8
作者：
Cho, Yoshitake;Ariga, Miyako;Takahashi, Shin-Ichiro
通讯作者：
Takahashi, Shin-Ichiro
影响因子：
7
作者：
Rasoamanana, Rojo;Darcel, Nicolas;Tome, Daniel
通讯作者：
Tome, Daniel