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

基本信息

批准号：
10597140
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
项目类别：
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/10597140
关键词：
ATP Synthesis Pathway Accelerometer Adult Ancillary Study Animals Attenuated Basal metabolic rate Bread Chronic Kidney Failure Circulation 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 Food Food Additives Freezing Funding Gene Expression Profile General Population Genes Health Heart Human Impairment 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 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 food preparation in vivo inorganic phosphate mitochondrial dysfunction oxidation primary outcome prospective respiratory secondary outcome soft drink translational study trend uptake urinary

项目摘要

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.

项目摘要/摘要无机磷酸盐（PI）过量使用作为防腐剂和加工中的风味增强食物。因此，美国25％的美国成年人在3-4倍的消费量中比建议的每日津贴高3-4倍定期。虽然饮食PI过量在慢性肾脏疾病中的影响良好研究了，它对普通人口的人类健康的影响尚未完全理解。我们最近在小鼠中的研究表明，饮食PI负载模仿美国成人消费水平会导致降低自发的运动活动，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。这些代谢变化是与涉及脂肪酸释放，转运和氧化的许多基因的下调有关。此外，我们对达拉斯心脏研究（DHS-3）进行的第三次检查的试点研究提供了支持动物数据是较高的饮食PI摄入量与体内较低的线粒体之间的牢固关联使用7-Tesla 31p磁共振光谱和运动过程中的氧气吸收功能为观察到。更重要的是，较高的饮食PI摄入量与胰岛素抵抗标记之间的关联，发现了包括较高的肝脏和肌肉脂肪含量。因此，我们提出了一项辅助研究已经对DHS进行了第三次检查，以测试饮食PI过量对体育锻炼和心肺健身。我们还将进行一项随机跨界研究，以确定是否肌肉线粒体功能和运动能力的磷毒性通过降低饮食PI恢复内容，与总能量摄入和其他营养成分无关。提议其他健康人的翻译研究有可能改变当前的临床实践范例通过将磷酸盐确定为一般人群中的关键可修改心脏代谢危险因素。