Institute for the Animal Production System, National Research Council, Naples, 80147, Italy.
Department of Science, Biomedical and Technology Science Section, University Roma Tre, Rome, 00146, Italy.
Mol Nutr Food Res. 2020 Aug;64(16):e2000541. doi: 10.1002/mnfr.202000541. Epub 2020 Jul 20.
Cholesterol homeostasis is crucial for brain functioning. Unhealthy nutrition can influence cerebral physiology, but the effect of western diets on brain cholesterol homeostasis, particularly at middle age, is unknown. Given the link between brain cholesterol alteration and beta amyloid production, the aim is to evaluate whether a diet rich in fat and fructose affects the protein network implicated in cholesterol synthesis and shuttling between glial cells and neurons, as well as crucial markers of beta amyloid metabolism.
Middle aged rats are fed a high fat-high fructose (HFF) or a control diet for 4 weeks. Inflammatory markers and cholesterol levels significantly increase in hippocampus of HFF rats. A higher activation of 3-hydroxy 3-methylglutaryl coenzyme-A reductase, coupled with lower levels of apolipoprotein E, LXR-beta, and lipoproteins receptors is measured in hippocampus from HFF rats. The alteration of critical players of cholesterol homeostasis is associated with increased level of amyloid precursor protein, presenilin 1, and nicastrin, and decreased level of insulin degrading enzyme.
Overall these data show that a western diet is associated with perturbation of cholesterol homeostasis in middle aged rats, mostly in hippocampus. This might trigger molecular events involved in the onset of neurodegenerative diseases.
胆固醇稳态对于大脑功能至关重要。不健康的营养会影响大脑的生理机能，但目前尚不清楚西式饮食对大脑胆固醇稳态的影响，尤其是在中年时期。鉴于大脑胆固醇改变与β淀粉样蛋白产生之间存在关联，本研究旨在评估富含脂肪和果糖的饮食是否会影响胆固醇合成和在神经胶质细胞与神经元之间转运的蛋白网络，以及β淀粉样蛋白代谢的关键标志物。
中年大鼠喂食高脂肪高果糖（HFF）饮食或对照饮食 4 周。HFF 组大鼠的海马体中炎症标志物和胆固醇水平显著升高。HFF 组大鼠的海马体中 3-羟-3-甲基戊二酰辅酶 A 还原酶的活性更高，载脂蛋白 E、LXR-β 和脂蛋白受体的水平更低。胆固醇稳态的关键调控因子的改变与淀粉样前体蛋白、早老素 1 和尼卡斯特林水平升高，胰岛素降解酶水平降低有关。
总的来说，这些数据表明，西式饮食与中年大鼠的胆固醇稳态失调有关，主要发生在海马体。这可能引发与神经退行性疾病发病相关的分子事件。
