Impact of Dietary Phosphate Excess on Exercise Capacity and Visceral Adiposity

项目摘要/摘要 在加工过程中，无机磷(PI)被过量用作防腐剂和风味增强剂 食物。因此，25%的美国成年人每天的PI消费是建议的每日津贴的3-4倍 定期的。虽然饮食中磷过量在慢性肾脏疾病中的影响一直很好- 经过研究，它对普通人群中的人类健康的影响仍然不完全清楚。我们最近 对小鼠的研究表明，模拟美国成人摄入量的膳食PI负荷会导致 正常时自发活动、运动能力和静息代谢率降低 小鼠骨骼肌线粒体功能受损和脂肪氧化。这些代谢变化是 与许多与脂肪酸释放、运输和氧化有关的基因下调有关。 此外，我们从达拉斯心脏研究(DHS-3)第三次检查中进行的初步研究为 动物数据表明，较高的膳食磷摄入量与较低的体内线粒体之间存在着强有力的联系 使用7-特斯拉31P磁共振波谱和运动时的摄氧量进行功能测试 观察到的。更重要的是，较高的膳食PI摄入量与胰岛素抵抗标记物之间的关联， 包括较高的肝脏和肌肉脂肪含量。因此，我们建议对 已经资助了国土安全部的第三次检查，以测试膳食磷过量对体力活动的影响 心肺健康。我们还将进行随机交叉研究，以确定这是否 降低饲料磷对肌肉线粒体功能和运动能力的影响 含量，这与总能量摄入量和其他营养成分无关。建议数 在其他健康人群中进行的翻译研究有可能改变目前的临床实践范例 通过在普通人群中确定磷酸盐是一个关键的可改变的心脏代谢危险因素。

Project Summary/Abstract Inorganic phosphate (Pi) is used in excess as a preservative and flavor enhancement in processed foods. Accordingly, 25% US adult consume Pi at 3-4 fold higher than the recommended daily allowance on a regular basis. While the impact of dietary Pi excess in the setting of chronic kidney disease has been well- studied, its impact on human health in the general population remains incompletely understood. Our recent study in mice demonstrated that dietary Pi loading that mimic the level of US adult consumption leads to reduced spontaneous locomotor activity, exercise capacity, and reduced resting metabolic rate when in normal mice by impairing skeletal muscle mitochondrial function and fat oxidation. These metabolic changes were related to downregulation of numerous genes involved in fatty acid release, transport, and oxidation. Furthermore, our pilot study from the third examination of the Dallas Heart Study (DHS-3) provided support for the animal data as a robust association between higher dietary Pi intake and lower in vivo mitochondrial function using 7-Tesla 31P magnetic resonance spectroscopy and oxygen uptake during exercise was observed. More importantly, an association between higher dietary Pi intake and markers of insulin resistance, including higher liver and muscle fat content was uncovered. Therefore, we propose an ancillary study to the already funded 3rd examination of the DHS to test the impact of dietary Pi excess on physical activity and cardiorespiratory fitness. We will also conduct a randomized crossover study to determine if this phosphotoxicity on the muscle mitochondrial function and exercise capacity is restored by lowering dietary Pi content, which is independent of total energy intake and other nutritional components. The proposed translational studies in otherwise healthy humans have the potential to shift current clinical practice paradigms by identifying phosphate as a key modifiable cardiometabolic risk factor in the general population.