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.

项目概要/摘要无机磷酸盐 (Pi) 被过量用作加工食品中的防腐剂和风味增强剂食物。因此，25% 的美国成年人摄入的 Pi 量比推荐每日摄入量高出 3-4 倍定期。虽然饮食中 Pi 过量对慢性肾脏病的影响已得到充分证实：经过研究，其对普通人群健康的影响仍不完全清楚。我们最近的对小鼠的研究表明，模仿美国成人消费水平的膳食 Pi 负荷会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通过损害骨骼肌线粒体功能和脂肪氧化来抑制小鼠。这些代谢变化是与涉及脂肪酸释放、运输和氧化的许多基因的下调有关。此外，我们的达拉斯心脏研究 (DHS-3) 第三次检查的试点研究为动物数据表明较高的膳食 Pi 摄入量与较低的体内线粒体之间存在强有力的关联使用 7-Tesla 31P 磁共振波谱和运动期间摄氧量的功能观察到。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存在关联，包括更高的肝脏和肌肉脂肪含量被发现。因此，我们建议进行一项辅助研究已经资助了国土安全部的第三次检查，以测试饮食中 Pi 过量对身体活动的影响，以及心肺健康。我们还将进行一项随机交叉研究，以确定这是否通过降低膳食 Pi 可以恢复对肌肉线粒体功能和运动能力的磷毒性含量，与总能量摄入和其他营养成分无关。拟议的在健康人类中进行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一个关键的可改变的心脏代谢危险因素。