Centre for Preclinical and Translational Medical Research, Central Research Facility, Sri Ramachandra Institute for Higher Education and Research, Chennai, India.
Centre for Biotechnology, Anna University, Chennai, India.
Nutr Neurosci. 2022 Jun;25(6):1277-1286. doi: 10.1080/1028415X.2020.1853413. Epub 2020 Dec 1.
Fructose-common sweetener, consumed in large quantities, is now known to be associated with various metabolic diseases. Recent reports suggest fructose's involvement in neurodegeneration, neurotoxicity, and neuroinflammation. But, its impact at cellular and subcellular level and on energy metabolism, especially, mitochondrial bioenergetics, in neurons is not known.
To study the adverse effects of high fructose in general, and on the mitochondria in a spinal cord motor neuron cell line, NSC-34, in vitro, and Caenorhabditis elegans in vivo.
NSC-34 was treated with 0.5%-5% of fructose for different time periods. Fructose's effect on cell viability (MTT assay), metabolic activity (XF24 Seahorse assays) and C. elegans, chronically fed with 5% fructose and alteration in healthspan/mitochondria was monitored.
In NSC-34: Fructose at 4-5% elicits 60% cell death. Unlike 1%, 5% fructose (F5%) decreased mitochondrial membrane potential by 29%. Shockingly, 6hours F5% treatment almost abolished mitochondrial respiration - basal-respiration (∨123%), maximal-respiration (∨ 95%) and spare-respiratory-capacity (∨ 83%) and ATP production (∨98%) as revealed by XF 24- Seahorse assays. But non - mitochondrial respiration was spared. F5% treatment for 48hrs resulted in the total shutdown of respiratory machinery including glycolysis. Chronic feeding of wildtype C.elegans to F5% throughout, shortened lifespan by ~3 days (∨ 17%), progressively reduced movement (day-2 -∨10.25%, day-5 -∨25% and day-10 -∨56%) and food intake with age (day-5-∨9% and day-10 -∨48%) and instigated mitochondrial swelling and disarray in their arrangement in adult worms body-wall muscle cells.
Chronic exposure to high fructose negatively impacts cell viability, mitochondrial function, basal glycolysis, and healthspan.
果糖是一种常见的甜味剂，虽然其在食品中被大量使用，但目前已知它与多种代谢疾病有关。最近的研究报告表明，果糖会导致神经退行性变、神经毒性和神经炎症。然而，其在细胞和亚细胞水平以及能量代谢，特别是神经元中线粒体生物能学方面的影响尚不清楚。
本研究旨在体外观察高果糖对脊髓运动神经元细胞系 NSC-34 以及体内秀丽隐杆线虫的线粒体的不良影响。
用 0.5%-5%的果糖处理 NSC-34 不同时间。通过 MTT 检测细胞活力、XF24 Seahorse 检测代谢活性以及慢性喂食 5%果糖的秀丽隐杆线虫健康寿命/线粒体的改变，监测果糖的作用。
在 NSC-34 中：4%-5%的果糖可引起 60%的细胞死亡。与 1%果糖不同，5%果糖（F5%）使线粒体膜电位降低 29%。令人震惊的是，6 小时的 F5%处理几乎完全消除了线粒体呼吸-基础呼吸（∨123%）、最大呼吸（∨95%）和备用呼吸能力（∨83%）和 ATP 产生（∨98%），这是通过 XF24-Seahorse 检测发现的。但是非线粒体呼吸得以保留。F5%处理 48 小时导致包括糖酵解在内的呼吸机制完全关闭。慢性喂食野生型秀丽隐杆线虫至 F5%，可将寿命缩短约 3 天（∨17%），随着年龄的增长，运动能力逐渐下降（第 2 天-∨10.25%，第 5 天-∨25%，第 10 天-∨56%），摄食量减少（第 5 天-∨9%，第 10 天-∨48%），并引发成虫体壁肌肉细胞中线粒体肿胀和排列紊乱。
慢性暴露于高果糖会对细胞活力、线粒体功能、基础糖酵解和健康寿命产生负面影响。
