Department of Animal Sciences and Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, Japan.
Department of Veterinary Medical Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo, Tokyo, Japan.
Sci Rep. 2020 Dec 17;10(1):22110. doi: 10.1038/s41598-020-79234-w.
Studies on animal models have demonstrated that feeding a low-arginine diet inhibits triacylglycerol (TAG) secretion from the liver, resulting in marked fatty liver development in rats. Here, we first showed that culturing hepatocytes in the medium mimicking the serum amino acid profile of low-arginine diet-fed rats induced TAG accumulation in the cells, indicating that the specific amino acid profile caused TAG accumulation in hepatocytes. Dietary adenine supplementation completely recovered hepatic TAG secretion and abolished hepatic TAG accumulation in rats. A comprehensive non-linear analysis revealed that inhibition of hepatic TAG accumulation by dietary adenine supplementation could be predicted using only serum amino acid concentration data. Comparison of serum amino acid concentrations indicated that histidine, methionine, and branched-chain amino acid (BCAA) concentrations were altered by adenine supplementation. Furthermore, when the serum amino acid profiles of low-arginine diet-fed rats were altered by modifying methionine or BCAA concentrations in their diets, their hepatic TAG accumulation was abolished. Altogether, these results suggest that an increase in methionine and BCAA levels in the serum in response to dietary arginine deficiency is a key causative factor for hepatic TAG accumulation, and dietary adenine supplementation could disrupt this phenomenon by altering serum amino acid profiles.
动物模型研究表明，低精氨酸饮食可抑制肝脏三酰甘油（TAG）的分泌，导致大鼠脂肪肝的显著发展。在这里，我们首先表明，在模拟低精氨酸饮食喂养大鼠血清氨基酸谱的培养基中培养肝细胞会导致细胞内 TAG 的积累，表明特定的氨基酸谱会导致肝细胞内 TAG 的积累。饮食腺嘌呤补充完全恢复了肝 TAG 的分泌，并消除了大鼠肝 TAG 的积累。全面的非线性分析表明，饮食腺嘌呤补充抑制肝 TAG 积累可以仅使用血清氨基酸浓度数据来预测。血清氨基酸浓度的比较表明，肝腺嘌呤补充会改变组氨酸、蛋氨酸和支链氨基酸（BCAA）的浓度。此外，当通过改变饮食中蛋氨酸或 BCAA 的浓度来改变低精氨酸饮食喂养大鼠的血清氨基酸谱时，其肝 TAG 的积累就会被消除。总之，这些结果表明，血清中蛋氨酸和 BCAA 水平的增加是对饮食精氨酸缺乏的一种关键的促发因素，而饮食腺嘌呤补充可以通过改变血清氨基酸谱来破坏这种现象。
