Departments of Psychiatry and Behavioral Science.
Cell Metabolism and Nutrition.
Adv Nutr. 2020 Nov 16;11(6):1489-1509. doi: 10.1093/advances/nmaa072.
Although excessive consumption of deep-fried foods is regarded as 1 of the most important epidemiological factors of lifestyle diseases such as Alzheimer's disease, type 2 diabetes, and obesity, the exact mechanism remains unknown. This review aims to discuss whether heated cooking oil-derived peroxidation products cause cell degeneration/death for the occurrence of lifestyle diseases. Deep-fried foods cooked in ω-6 PUFA-rich vegetable oils such as rapeseed (canola), soybean, sunflower, and corn oils, already contain or intrinsically generate "hydroxynonenal" by peroxidation. As demonstrated previously, hydroxynonenal promotes carbonylation of heat-shock protein 70.1 (Hsp70.1), with the resultant impaired ability of cells to recycle damaged proteins and stabilize the lysosomal membrane. Until now, the implication of lysosomal/autophagy failure due to the daily consumption of ω-6 PUFA-rich vegetable oils in the progression of cell degeneration/death has not been reported. Since the "calpain-cathepsin hypothesis" was formulated as a cause of ischemic neuronal death in 1998, its relevance to Alzheimer's neuronal death has been suggested with particular attention to hydroxynonenal. However, its relevance to cell death of the hypothalamus, liver, and pancreas, especially related to appetite/energy control, is unknown. The hypothalamus senses information from both adipocyte-derived leptin and circulating free fatty acids. Concentrations of circulating fatty acid and its oxidized form, especially hydroxynonenal, are increased in obese and/or aged subjects. As overactivation of the fatty acid receptor G-protein coupled receptor 40 (GPR40) in response to excessive or oxidized fatty acids in these subjects may lead to the disruption of Ca2+ homeostasis, it should be evaluated whether GPR40 overactivation contributes to diverse cell death. Here, we describe the molecular implication of ω-6 PUFA-rich vegetable oil-derived hydroxynonenal in lysosomal destabilization leading to cell death. By oxidizing Hsp70.1, both the dietary PUFA- (exogenous) and the membrane phospholipid- (intrinsic) peroxidation product "hydroxynonenal," when combined, may play crucial roles in the occurrence of diverse lifestyle diseases including Alzheimer's disease.
尽管过量食用油炸食品被认为是阿尔茨海默病、2 型糖尿病和肥胖等生活方式疾病的最重要的流行病学因素之一，但确切的机制仍不清楚。本综述旨在讨论加热食用油衍生的过氧化物是否会导致细胞变性/死亡，从而引发生活方式疾病。用富含 ω-6PUFA 的植物油（如油菜籽、大豆、葵花籽油和玉米油）煎炸的食物已经通过过氧化反应产生或固有地生成“羟壬烯醛”。正如之前所证明的，羟壬烯醛促进热休克蛋白 70.1（Hsp70.1）的羰基化，从而导致细胞回收受损蛋白质和稳定溶酶体膜的能力受损。到目前为止，由于每天食用富含 ω-6PUFA 的植物油，导致溶酶体/自噬功能障碍，从而导致细胞变性/死亡的进展情况尚未报道。自 1998 年提出“钙蛋白酶-组织蛋白酶假说”作为缺血性神经元死亡的原因以来，人们特别关注羟壬烯醛，认为其与阿尔茨海默病神经元死亡有关。然而，其与下丘脑、肝脏和胰腺细胞死亡的相关性，特别是与食欲/能量控制相关的细胞死亡的相关性尚不清楚。下丘脑感知来自脂肪细胞衍生的瘦素和循环游离脂肪酸的信息。肥胖和/或年龄较大的受试者中循环脂肪酸及其氧化形式（特别是羟壬烯醛）的浓度增加。由于这些受试者中过量或氧化的脂肪酸对脂肪酸受体 G 蛋白偶联受体 40（GPR40）的过度激活可能导致钙稳态的破坏，因此应该评估 GPR40 的过度激活是否导致不同的细胞死亡。在这里，我们描述了富含 ω-6PUFA 的植物油衍生的羟壬烯醛在溶酶体不稳定导致细胞死亡中的分子意义。通过氧化 Hsp70.1，膳食 PUFA（外源性）和膜磷脂（内源性）过氧化产物“羟壬烯醛”结合在一起，可能在包括阿尔茨海默病在内的多种生活方式疾病的发生中发挥关键作用。
