Impact of Dietary Phosphate Excess on Exercise Capacity and Visceral Adiposity

膳食磷酸盐过量对运动能力和内脏肥胖的影响

• 批准号: 10464465
• 负责人: Jarett D Berry
• 金额: $ 80.53万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10464465
• 关键词: ATP Synthesis Pathway; Accelerometer; Adult; Ancillary Study; Animals; Attenuated; Basal metabolic rate; Blood Circulation; Bread; Chronic Kidney Failure; Consumption; Cross-Over Studies; Cross-Over Trials; Data; Diet; Dietary Practices; Dietary Questionnaires; Dietary intake; Down-Regulation; Energy Intake; Etiology; Excretory function; Exercise; Fatty Acids; Fatty acid glycerol esters; Fibroblast Growth Factor; Food; Food Additives; Freezing; Funding; Gene Expression Profile; General Population; Genes; Health; Heart; Human; Impairment; Institutes; Insulin Resistance; Intake; Knowledge; Liver; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Meat; Metabolic; Metabolism; Mitochondria; Motor Activity; Mus; Muscle; Muscle Mitochondria; Nutritional; Obesity; Oxygen; Participant; Pathogenicity; Physical activity; Pilot Projects; Process; Public Health; Randomized; Recommendation; Recommended Daily Allowances; Rest; Risk Factors; Series; Serum; Skeletal Muscle; Testing; Theoretical model; Visceral; Visceral fat; Work; adverse outcome; animal data; base; carbohydrate metabolism; cardiometabolic risk; cardiometabolism; cardiorespiratory fitness; cardiovascular health; clinical practice; dietary; dietary excess; evidence based guidelines; exercise capacity; exercise intolerance; fast food; fatty acid oxidation; fibroblast growth factor 23; in vivo; inorganic phosphate; mitochondrial dysfunction; oxidation; primary outcome; prospective; respiratory; secondary outcome; soft drink; translational study; trend; uptake; urinary

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.

项目总结/摘要 无机磷酸盐（Pi）在加工过程中过量用作防腐剂和风味增强剂。 食品因此，25%的美国成年人摄入的Pi比推荐的每日摄入量高3-4倍， 定期.虽然饮食中过量的Pi对慢性肾脏疾病的影响已经很好- 尽管已经进行了研究，但其对一般人群健康的影响仍然没有完全了解。我们最近 对小鼠的研究表明，模拟美国成人消费水平的膳食Pi负荷导致 正常情况下，自发运动活动、运动能力和静息代谢率降低 小鼠通过损害骨骼肌线粒体功能和脂肪氧化。这些代谢变化是 与参与脂肪酸释放、转运和氧化的许多基因的下调有关。 此外，我们在达拉斯心脏研究（DHS-3）第三次检查中的初步研究为以下方面提供了支持： 动物数据显示较高的膳食Pi摄入量和较低的体内线粒体 使用7特斯拉31 P磁共振波谱和运动期间的氧摄取功能， 观察更重要的是，较高的膳食Pi摄入量与胰岛素抵抗标志物之间的关联， 包括更高的肝脏和肌肉脂肪含量。因此，我们建议进行辅助研究， 已经资助了DHS的第三次检查，以测试膳食Pi过量对身体活动的影响， 心肺适能我们还将进行一项随机交叉研究，以确定 通过降低饮食中的Pi，可以恢复对肌肉线粒体功能和运动能力的磷毒性 含量，这是独立的总能量摄入量和其他营养成分。拟议 在其他健康人群中的转化研究有可能改变当前的临床实践范式 通过将磷酸盐确定为普通人群中关键的可改变的心脏代谢风险因素。