PDF(Pubmed)
Abstract：
Obesity is a risk factor for highly prevalent age-related neurodegenerative diseases, the pathogenesis of whichinvolves mitochondrial dysfunction and protein oxidative damage. Lipoxidation, driven by high levels of peroxidizable unsaturated fatty acids and low antioxidant protection of the brain, stands out as a significant risk factor. To gain information on the relationship between obesity and brain molecular damage, in a porcine model of obesity we evaluated (1) the level of mitochondrial respiratory chain complexes, as the main source of free radical generation, by Western blot; (2) the fatty acid profile by gas chromatography; and (3) the oxidative modification of proteins by mass spectrometry. The results demonstrate a selectively higher amount of the lipoxidation-derived biomarker malondialdehyde-lysine (MDAL) (34% increase) in the frontal cortex, and positive correlations between MDAL and LDL levels and body weight. No changes were observed in brain fatty acid profile by the high-fat diet, and the increased lipid peroxidative modification was associated with increased levels of mitochondrial complex I (NDUFS3 and NDUFA9 subunits) and complex II (flavoprotein). Interestingly, introducing n3 fatty acids and a probiotic in the high-fat diet prevented the observed changes, suggesting that dietary components can modulate protein oxidative modification at the cerebral level and opening new possibilities in neurodegenerative diseases\' prevention.
摘要：
肥胖是一个高度流行的年龄相关的神经退行性疾病的危险因素，其发病机制涉及线粒体功能障碍和蛋白质氧化损伤。脂肪氧化,由高水平的可过氧化不饱和脂肪酸和低抗氧化保护的大脑驱动，作为一个重要的风险因素。为了获得肥胖与脑分子损伤之间关系的信息，在猪肥胖模型中，我们评估了（1）线粒体呼吸链复合物的水平，作为自由基产生的主要来源，通过蛋白质印迹;(2)通过气相色谱法的脂肪酸谱;和(3)通过质谱法的蛋白质的氧化修饰。结果表明额叶皮质中选择性地更高量的脂氧化衍生的生物标志物丙二醛-赖氨酸（MDAL）（增加34％），MDAL和LDL水平与体重呈正相关。高脂肪饮食没有观察到大脑脂肪酸谱的变化，脂质过氧化修饰的增加与线粒体复合物I（NDUFS3和NDUFA9亚基）和复合物II（黄素蛋白）的水平增加有关。有趣的是,在高脂饮食中引入n3脂肪酸和益生菌阻止了观察到的变化，这表明膳食成分可以调节大脑水平的蛋白质氧化修饰，并为神经退行性疾病的预防开辟了新的可能性。
