Department of Environmental Health and Center for Environmental Genetics, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, OH 45267, USA.
Neurosci Lett. 2013 Aug 26;548:159-64. doi: 10.1016/j.neulet.2013.05.061. Epub 2013 Jun 6.
In humans and experimental animals, protein-enriched diets are beneficial for weight management, muscle development, managing early stage insulin resistance and overall health. Previous studies have shown that in mice consuming a high fat diet, whey protein isolate (WPI) reduced hepatosteatosis and insulin resistance due in part to an increase in basal metabolic rate. In the current study, we examined the ability of WPI to increase energy metabolism in mouse brain. Female C57BL/6J mice were fed a normal AIN-93M diet for 12 weeks, with (WPI group) or without (Control group) 100g WPI/L drinking water. In WPI mice compared to controls, the oxidative stress biomarkers malondialdehyde and 4-hydroxyalkenals were 40% lower in brain homogenates, and the production of hydrogen peroxide and superoxide were 25-35% less in brain mitochondria. Brain mitochondria from WPI mice remained coupled, and exhibited higher rates of respiration with proportionately greater levels of cytochromes a+a3 and c+c1. These results suggested that WPI treatment increased the number or improved the function of brain mitochondria. qRT-PCR revealed that the gene encoding a master regulator of mitochondrial activity and biogenesis, Pgc-1alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) was elevated 2.2-fold, as were the PGC-1alpha downstream genes, Tfam (mitochondrial transcription factor A), Gabpa/Nrf-2a (GA-binding protein alpha/nuclear respiratory factor-2a), and Cox-6a1 (cytochrome oxidase-6a1). Each of these genes had twice the levels of transcript in brain tissue from WPI mice, relative to controls. There was no change in the expression of the housekeeping gene B2mg (beta-2 microglobulin). We conclude that dietary whey protein decreases oxidative stress and increases mitochondrial activity in mouse brain. Dietary supplementation with WPI may be a useful clinical intervention to treat conditions associated with oxidative stress or diminished mitochondrial activity in the brain.
在人类和实验动物中，富含蛋白质的饮食有益于体重管理、肌肉发育、早期胰岛素抵抗管理以及整体健康。先前的研究表明，在食用高脂肪饮食的小鼠中，乳清蛋白分离物（WPI）减少了肝脂肪变性和胰岛素抵抗，部分原因是基础代谢率的增加。在本研究中，我们研究了 WPI 增加小鼠大脑能量代谢的能力。雌性 C57BL/6J 小鼠用正常的 AIN-93M 饮食喂养 12 周，用（WPI 组）或不用（对照组）含 100g WPI/L 的饮用水。与对照组相比，WPI 组小鼠的大脑匀浆中的氧化应激生物标志物丙二醛和 4-羟基烯醛降低了 40%，脑线粒体中产生的过氧化氢和超氧化物减少了 25-35%。WPI 组小鼠的脑线粒体保持偶联，呼吸速率更高，细胞色素 a+a3 和 c+c1 的比例也更高。这些结果表明，WPI 处理增加了脑线粒体的数量或改善了其功能。qRT-PCR 显示，编码线粒体活性和生物发生的主调节因子 Pgc-1alpha（过氧化物酶体增殖物激活受体-γ共激活因子-1alpha）的基因表达升高了 2.2 倍，其下游基因 Tfam（线粒体转录因子 A）、Gabpa/Nrf-2a（GA 结合蛋白 alpha/核呼吸因子-2a）和 Cox-6a1（细胞色素氧化酶-6a1）也是如此。WPI 组小鼠大脑组织中这些基因的转录水平均为对照组的两倍。管家基因 B2mg（β-2 微球蛋白）的表达没有变化。我们得出结论，饮食乳清蛋白可降低小鼠大脑中的氧化应激并增加线粒体活性。饮食补充 WPI 可能是一种有用的临床干预措施，可用于治疗与大脑氧化应激或线粒体活性降低相关的疾病。
