Toxicity of sugars and identification of markers for pathophysiology in citrin deficiency leading to development of novel therapeutics

我们建立了一种瓜氨酸缺乏导致新生儿期新生儿肝内胆汁淤积（NICCD）和成年期成年发病的II型瓜氨酸血症（CTLN 2）的模型小鼠。我们发现，给小鼠施用糖会导致恶化，如高氨血症。从代谢组学分析，我们发现，糖的管理诱导肝甘油-3-磷酸（G3 P），这是有用的柠檬酸缺乏症的生物标志物显着增加。我们发现，饮食从高蛋白质到低蛋白质的变化诱导体重下降，模仿疾病中的生长迟缓或消瘦，并且在低蛋白质饮食中添加物质如蛋白质、氨基酸、丙酮酸和中链甘油三酯增加食物摄入量和体重。

We have established a model mouse of citrin deficiency causing neonatal intrahepatic cholestasis(NICCD) at neonatal period and adult-onset type II citrullinemia(CTLN2) at adult age. We showed that administration of sugars to the mice caused deterioration such as hyperammonemia. From the metabolomics analysis, we found that administration of sugars induced a marked increase in hepatic glycerol-3-phosphate(G3P), which is useful as a biomarker for citrin deficiency. We found that dietary change from high protein to low protein induced a decreased body weight, mimicking growth retardation or skinniness in the disease and that addition of substance such as protein, amino acids, pyruvate and medium-chain triglyceride to the low-protein diet increased food intake and body weight.