School of Biotechnology and Biomolecular Sciences, Sydney, Australia.
Bioanalytical Mass Spectrometry Facility, Mark Wainwright Analytical Center, University of New South Wales, Sydney, Australia.
J Gerontol A Biol Sci Med Sci. 2019 Sep 15;74(10):1564-1572. doi: 10.1093/gerona/glx246.
Optimizing dietary macronutrients benefits the prevention and management of many human diseases but there is conflicting dietary advice for Parkinson's disease (PD), and no single strategy is universally recommended. Recently, it was shown that dietary stearic acid (C18:0) improves survival and mitochondrial functions in the parkin null Drosophila model of PD. Here, we incorporate stearic acid into high protein and high carbohydrate diets and study survival, climbing ability, mitochondrial membrane potential, respiration, basal reactive oxygen species, and conduct lipidomics assays. We observed that parkin null flies showed improvement in all assays tested when stearic acid was added to the high protein diet but not to the high carbohydrate diet. When lipid proportion was examined, we observed higher levels in flies fed the high protein diet with stearic acid diet and the high carbohydrate diet. Unexpectedly, free levels of fatty acids exhibited opposite trend. Combined, these data suggest that dietary Protein: Carbohydrate ratio and stearic acid influences levels of bound fatty acids. The mechanisms that influence free and bound fatty-acid levels remain to be explored, but one possible explanation is that breakdown products can bind to membranes and improve the mitochondrial functions of parkin null flies.
优化饮食中的宏量营养素有益于预防和治疗许多人类疾病，但针对帕金森病（PD）的饮食建议存在冲突，没有一种单一的策略被普遍推荐。最近的研究表明，饮食中的硬脂酸（C18:0）可改善帕金森病 parkin 基因敲除果蝇模型的生存和线粒体功能。在这里，我们将硬脂酸纳入高蛋白和高碳水化合物饮食中，并研究了生存、攀爬能力、线粒体膜电位、呼吸、基础活性氧和脂质组学分析。我们发现，当硬脂酸添加到高蛋白饮食中时，parkin 基因敲除果蝇在所有测试中都表现出改善，但在高碳水化合物饮食中则没有。当检查脂质比例时，我们观察到喂食高蛋白饮食加硬脂酸饮食和高碳水化合物饮食的果蝇中的水平更高。出乎意料的是，游离脂肪酸的水平则呈现相反的趋势。综合这些数据表明，饮食中的蛋白质：碳水化合物比例和硬脂酸影响结合脂肪酸的水平。影响游离和结合脂肪酸水平的机制仍有待探索，但一种可能的解释是，分解产物可以与膜结合，改善 parkin 基因敲除果蝇的线粒体功能。
