背景:增加果糖作为添加糖的消耗代表了一个主要的健康问题。由于下丘脑功能的复杂性和多样性,我们的目标是指出在整个青春期由富含糖的饮食引发的早期分子改变,并验证它们的持久性,直到年轻的成年阶段。
方法:30日龄大鼠接受高果糖或对照饮食3周。在实验期结束时,将处理过的动物切换到对照饮食,再持续3周,然后与整个实验期间饲喂对照饮食的比较进行分析。
结果:定量蛋白质组学鉴定出19种差异代表的蛋白质,在对照组和果糖喂养组之间,属于中间丝细胞骨架,神经丝,孔复合物和线粒体呼吸链复合物。蛋白质印迹分析证实了蛋白质组数据,证明线粒体呼吸复合物和电压依赖性阴离子通道1(线粒体生物发生的共调节因子PGC-1α)的丰度降低,和果糖喂养大鼠神经丝α-internexin的蛋白质亚基。还检测到饮食相关的下丘脑炎症。最后,脑源性神经营养因子及其高亲和力受体TrkB,以及突触素,突触蛋白,糖喂养大鼠的突触后蛋白PSD-95降低。值得注意的是,在切换到对照饮食后,所有蛋白质水平的失调被完全挽救.
结论:青春期大鼠短期富含果糖的饮食会诱发下丘脑炎症,并高度影响线粒体和细胞骨架区室,以及脑功能的特定标志物水平;将动物转换为对照饮食后,上述报道的效果会恢复。
BACKGROUND: The enhanced consumption of fructose as added sugar represents a major health concern. Due to the complexity and multiplicity of hypothalamic functions, we aim to point out early molecular alterations triggered by a sugar-rich diet throughout adolescence, and to verify their persistence until the young adulthood phase.
METHODS: Thirty days old rats received a high-fructose or control diet for 3 weeks. At the end of the experimental period, treated animals were switched to the control diet for further 3 weeks, and then analyzed in comparison with those that were fed the control diet for the entire experimental period.
RESULTS: Quantitative proteomics identified 19 differentially represented proteins, between control and fructose-fed groups, belonging to intermediate filament cytoskeleton, neurofilament, pore complex and mitochondrial respiratory chain complexes. Western blotting analysis confirmed proteomic data, evidencing a decreased abundance of mitochondrial respiratory complexes and voltage-dependent anion channel 1, the coregulator of mitochondrial biogenesis PGC-1α, and the protein subunit of neurofilaments α-internexin in fructose-fed rats. Diet-associated hypothalamic inflammation was also detected. Finally, the amount of brain-derived neurotrophic factor and its high-affinity receptor TrkB, as well as of synaptophysin, synaptotagmin, and post-synaptic protein PSD-95 was reduced in sugar-fed rats. Notably, deregulated levels of all proteins were fully rescued after switching to the control diet.
CONCLUSIONS: A short-term fructose-rich diet in adolescent rats induces hypothalamic inflammation and highly affects mitochondrial and cytoskeletal compartments, as well as the level of specific markers of brain function; above-reported effects are reverted after switching animals to the control diet.