用硝酸盐治疗而非亚硝酸盐治疗，可降低运动中的耗氧量，降低糖酵解中间产物，增加运动斑马鱼的脂肪酸代谢物。

Treatment with Nitrate, but Not Nitrite, Lowers the Oxygen Cost of Exercise and Decreases Glycolytic Intermediates While Increasing Fatty Acid Metabolites in Exercised Zebrafish.

机构信息

Department of Pharmaceutical Sciences, Oregon State University, Corvallis, OR, USA.

Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.

出版信息

J Nutr. 2019 Dec 1;149(12):2120-2132. doi: 10.1093/jn/nxz202.

DOI:10.1093/jn/nxz202

PMID:31495890

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6887948/

Abstract

BACKGROUND

Dietary nitrate improves exercise performance by reducing the oxygen cost of exercise, although the mechanisms responsible are not fully understood.

OBJECTIVES

We tested the hypothesis that nitrate and nitrite treatment would lower the oxygen cost of exercise by improving mitochondrial function and stimulating changes in the availability of metabolic fuels for energy production.

METHODS

We treated 9-mo-old zebrafish with nitrate (sodium nitrate, 606.9 mg/L), nitrite (sodium nitrite, 19.5 mg/L), or control (no treatment) water for 21 d. We measured oxygen consumption during a 2-h, strenuous exercise test; assessed the respiration of skeletal muscle mitochondria; and performed untargeted metabolomics on treated fish, with and without exercise.

RESULTS

Nitrate and nitrite treatment increased blood nitrate and nitrite levels. Nitrate treatment significantly lowered the oxygen cost of exercise, as compared with pretreatment values. In contrast, nitrite treatment significantly increased oxygen consumption with exercise. Nitrate and nitrite treatments did not change mitochondrial function measured ex vivo, but significantly increased the abundances of ATP, ADP, lactate, glycolytic intermediates (e.g., fructose 1,6-bisphosphate), tricarboxylic acid (TCA) cycle intermediates (e.g., succinate), and ketone bodies (e.g., β-hydroxybutyrate) by 1.8- to 3.8-fold, relative to controls. Exercise significantly depleted glycolytic and TCA intermediates in nitrate- and nitrite-treated fish, as compared with their rested counterparts, while exercise did not change, or increased, these metabolites in control fish. There was a significant net depletion of fatty acids, acyl carnitines, and ketone bodies in exercised, nitrite-treated fish (2- to 4-fold), while exercise increased net fatty acids and acyl carnitines in nitrate-treated fish (1.5- to 12-fold), relative to their treated and rested counterparts.

CONCLUSIONS

Nitrate and nitrite treatment increased the availability of metabolic fuels (ATP, glycolytic and TCA intermediates, lactate, and ketone bodies) in rested zebrafish. Nitrate treatment may improve exercise performance, in part, by stimulating the preferential use of fuels that require less oxygen for energy production.

摘要

背景

膳食硝酸盐通过降低运动的氧气成本来提高运动表现，尽管其相关机制尚未完全阐明。

目的

我们检验了这样一个假设，即硝酸盐和亚硝酸盐处理通过改善线粒体功能和刺激代谢燃料可用性的变化来为能量产生提供燃料，从而降低运动的氧气成本。

方法

我们用硝酸盐（硝酸钠，606.9mg/L）、亚硝酸盐（亚硝酸钠，19.5mg/L）或对照（不处理）水对 9 月龄斑马鱼处理 21 天。我们在 2 小时的剧烈运动测试中测量了耗氧量；评估了骨骼肌线粒体的呼吸功能；并对经处理的鱼进行了非靶向代谢组学分析，包括运动前后的鱼。

结果

硝酸盐和亚硝酸盐处理增加了血液中的硝酸盐和亚硝酸盐水平。与预处理值相比，硝酸盐处理显著降低了运动的氧气成本。相比之下，亚硝酸盐处理在运动时显著增加了耗氧量。硝酸盐和亚硝酸盐处理并没有改变体外测量的线粒体功能，但却使 ATP、ADP、乳酸、糖酵解中间产物（如 1,6-二磷酸果糖）、三羧酸（TCA）循环中间产物（如琥珀酸）和酮体（如 β-羟丁酸）的丰度分别增加了 1.8-3.8 倍，与对照组相比。与休息时的鱼相比，运动显著消耗了硝酸盐和亚硝酸盐处理鱼的糖酵解和 TCA 中间产物，但运动没有改变或增加对照组鱼的这些代谢物。与休息时的鱼相比，运动使硝态氮处理鱼的脂肪酸、酰基辅酶 A 和酮体的净消耗增加了 2-4 倍（2-4 倍），而运动使硝态氮处理鱼的脂肪酸和酰基辅酶 A 的净消耗增加了 1.5-12 倍（1.5-12 倍），与它们的治疗和休息对照物相比。