High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice
High-Phosphate Diet Induces Exercise Intolerance and Impairs Fatty Acid Metabolism in Mice
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DOI：
10.1161/circulationaha.118.037550
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发表时间：
2019-03-12
期刊：
影响因子：
37.8
通讯作者：
Vongpatanasin, Wanpen
中科院分区：
文献类型：
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作者：
Peri-Okonny, Poghni;Baskin, Kedryn K.;Vongpatanasin, Wanpen
背景：无机磷酸盐（Pi）在西方饮食中被广泛用作防腐剂和增味剂。缺乏身体活动是西方社会的一个共同特征，与心血管疾病发病率和死亡率的增加有关。目前尚不清楚饮食中的Pi过量是否会导致运动不耐受和身体inactivity.METHODS：为了确定Pi过量与人类身体活动之间的关系，我们评估了DHS-2（达拉斯心脏研究2期）参与者在调整相关变量后血清Pi和活动记录仪确定的身体活动水平以及心脏磁共振成像左心室功能之间的关系。为了确定膳食Pi对运动能力的直接影响，在运动平板试验期间测量了C57/BL 6小鼠的摄氧量、血清非酯化脂肪酸和葡萄糖，所述小鼠喂食高Pi（2%）或正常Pi（0.6%）饮食12周。为了确定Pi对肌肉代谢和参与脂肪酸代谢的基因表达的直接影响，在使分化的C2 C12肌管经受含有1至3 mmol/L Pi的培养基后进行另外的研究（pH 7.0）以模拟体内磷酸盐条件。在DHS-2的参与者中（n=1603），较高的血清Pi与中度至剧烈体力活动的时间减少（P=0.01）和久坐时间增加（P=0.004）独立相关。血清Pi与左心室射血分数或容积之间无相关性。在动物研究中，与对照饮食相比，食用高Pi饮食12周并没有改变体重或左心室功能，但减少了最大摄氧量、跑步机持续时间、自发运动活动、脂肪氧化和脂肪酸水平，并导致参与脂肪酸合成、释放和氧化的基因下调，包括Fabp 4、Hsl、Fasn和Ppar。肌肉。通过孵育C2 C12 myotubes与高Pi medium.CONCLUSIONS：我们的数据表明，饮食中的Pi过量对骨骼肌脂肪酸代谢和运动能力的不利影响是独立的肥胖和心脏收缩功能。膳食Pi可能代表了一个新的和可修改的目标，以减少与西方饮食相关的身体活动。
BACKGROUND: Inorganic phosphate (Pi) is used extensively as a preservative and a flavor enhancer in the Western diet. Physical inactivity, a common feature of Western societies, is associated with increased cardiovascular morbidity and mortality. It is unknown whether dietary Pi excess contributes to exercise intolerance and physical inactivity.METHODS: To determine an association between Pi excess and physical activity in humans, we assessed the relationship between serum Pi and actigraphy-determined physical activity level, as well as left ventricular function by cardiac magnetic resonance imaging, in DHS-2 (Dallas Heart Study phase 2) participants after adjusting for relevant variables. To determine direct effects of dietary Pi on exercise capacity, oxygen uptake, serum nonesterified fatty acid, and glucose were measured during exercise treadmill test in C57/BL6 mice fed either a high-Pi (2%) or normal-Pi (0.6%) diet for 12 weeks. To determine the direct effect of Pi on muscle metabolism and expression of genes involved in fatty acid metabolism, additional studies in differentiated C2C12 myotubes were conducted after subjecting to media containing 1 to 3 mmol/L Pi (pH 7.0) to simulate in vivo phosphate conditions.RESULTS: In participants of the DHS-2 (n=1603), higher serum Pi was independently associated with reduced time spent in moderate to vigorous physical activity (P=0.01) and increased sedentary time (P=0.004). There was no association between serum Pi and left ventricular ejection fraction or volumes. In animal studies, compared with the control diet, consumption of high-Pi diet for 12 weeks did not alter body weight or left ventricular function but reduced maximal oxygen uptake, treadmill duration, spontaneous locomotor activity, fat oxidation, and fatty acid levels and led to downregulation of genes involved in fatty acid synthesis, release, and oxidation, including Fabp4, Hsl, Fasn, and Ppar., in muscle. Similar results were recapitulated in vitro by incubating C2C12 myotubes with high-Pi media.CONCLUSIONS: Our data demonstrate a detrimental effect of dietary Pi excess on skeletal muscle fatty acid metabolism and exercise capacity that is independent of obesity and cardiac contractile function. Dietary Pi may represent a novel and modifiable target to reduce physical inactivity associated with the Western diet.