Specific regions of the brain are capable of fructose metabolism.
Specific regions of the brain are capable of fructose metabolism.
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DOI：
10.1016/j.brainres.2016.12.022
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发表时间：
2017-02-15
期刊：
影响因子：
2.9
通讯作者：
Tolan DR
中科院分区：
文献类型：
--
作者：
Oppelt SA;Zhang W;Tolan DR
西方饮食中的高果糖摄入与肥胖和代谢综合征并发症等疾病状态相关，包括II型糖尿病，慢性肾脏疾病和非酒精性脂肪酸肝病。肝脏和肾脏负责代谢40-60%摄入的果糖，而剩余果糖的生理命运仍然知之甚少。果糖的主要代谢途径包括果糖转运溶质样载体转运蛋白2a（SLC 2a或GLUT），包括GLUT 5和GLUT 9、己酮糖激酶（KHK）和醛缩酶。对编码这些蛋白质（分别为p53 5、p53 9、khk和aldoC）的基因表达的生物信息学分析鉴定了能够进行这种果糖代谢的其他器官。该分析预测脑、淋巴网状组织、胎盘和生殖组织可能是果糖代谢的额外器官。虽然这些基因在肝脏中的表达最高，但预测大脑中这些基因的表达水平与肾脏相似。成年小鼠大脑冠状切片的RNA原位杂交验证了p53 5、p53 9、khk和aldoC的计算机表达，并显示在大脑的许多区域中表达，其中在小脑、海马、皮质和嗅球中的表达最显著。这些脑区的解剖样品显示KHK和醛缩酶酶活性是肝脏中浓度的5-10倍。此外，这些脑区的果糖氧化速率是肝脏切片的15-150倍，证实了生物信息学预测和原位杂交数据。这表明，大脑中以前未被重视的区域除了葡萄糖外，还可以使用果糖来产生能量。
High fructose consumption in the Western diet correlates with disease states such as obesity and metabolic syndrome complications, including type II diabetes, chronic kidney disease, and nonalcoholic fatty acid liver disease. Liver and kidneys are responsible for metabolism of 40–60% of ingested fructose, while the physiological fate of the remaining fructose remains poorly understood. The primary metabolic pathway for fructose includes the fructose-transporting solute-like carrier transport proteins 2a (SLC2a or GLUT), including GLUT5 and GLUT9, ketohexokinase (KHK), and aldolase. Bioinformatic analysis of gene expression encoding these proteins (glut5, glut9, khk, and aldoC, respectively) identifies other organs capable of this fructose metabolism. This analysis predicts brain, lymphoreticular tissue, placenta, and reproductive tissues as possible additional organs for fructose metabolism. While expression of these genes is highest in liver, the brain is predicted to have expression levels of these genes similar to kidney. RNA in situ hybridization of coronal slices of adult mouse brains validate the in silico expression of glut5, glut9, khk, and aldoC, and show expression across many regions of the brain, with the most notable expression in the cerebellum, hippocampus, cortex, and olfactory bulb. Dissected samples of these brain regions show KHK and aldolase enzyme activity 5–10 times the concentration of that in liver. Furthermore, rates of fructose oxidation in these brain regions are 15–150 times that of liver slices, confirming the bioinformatics prediction and in situ hybridization data. This suggests that previously unappreciated regions across the brain can use fructose, in addition to glucose, for energy production.