Metabolic Architecture of Acute Exercise Response in Middle-Aged Adults in the Community.
Metabolic Architecture of Acute Exercise Response in Middle-Aged Adults in the Community.
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DOI：
10.1161/circulationaha.120.050281
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发表时间：
2020-11-17
期刊：
影响因子：
37.8
通讯作者：
Lewis GD
中科院分区：
文献类型：
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作者：
Nayor M;Shah RV;Miller PE;Blodgett JB;Tanguay M;Pico AR;Murthy VL;Malhotra R;Houstis NE;Deik A;Pierce KA;Bullock K;Dailey L;Velagaleti RS;Moore SA;Ho JE;Baggish AL;Clish CB;Larson MG;Vasan RS;Lewis GD
虽然定期锻炼与心血管疾病（CVD）和死亡率的风险降低有关，但运动介导的健康益处的机制仍不清楚。我们在急性运动前后使用代谢物分析来描绘人类运动反应模式的代谢结构。对FHS参与者（年龄53±8岁，63%为女性）进行了心脏运动试验（CPET）和代谢产物分析，在静息时（n=471）和运动高峰时（n=411）抽血。在5%的错误发现率（FDR）下，我们观察到588种测量代谢物中的502种从休息到峰值运动（运动持续时间11.9±2.1分钟）的循环水平变化。变化包括与胰岛素抵抗有关的代谢物减少（谷氨酸− 29%，P=1.5x10−55，二甲基胍基戊酸− 18%，P=5.8x10−18），以及与脂解相关的代谢物增加（1-甲基烟酰胺，+33%，P=6.1x10−67），一氧化氮生物利用度（精氨酸/鸟氨酸+瓜氨酸，+29%，P=2.8x10−169）和脂肪布朗宁（12，13-二羟基-9Z-十八碳烯酸+26%，P=7.4x10−38），以及其他与心脏代谢风险相关的途径。我们在单独的FHS复制样本（n=783，年龄54±8岁，51%女性）中测定了177种代谢物，并在5%FDR下观察到164种代谢物（92.6%）的一致变化。运动诱导的代谢物变化与运动量（峰值工作量）、性别和体重指数（BMI）呈负相关。在BMI较高的个体中，某些代谢物的有利波动减弱，而在女性中，尽管运动量较少，但选择的心脏保护代谢物的波动更大。不同的运动前代谢物水平与健身的不同生理维度相关（例如，呼吸效率、运动血压、峰值VO 2）。我们确定了运动反应模式的四种代谢物特征，然后在一个单独的队列中进行了分析（Fragmentary Offspring研究; n=2045，年龄55±10岁，51%为女性），其中两种与中位随访23.1年的总死亡率相关（两种均P≤0.003）。在社区居民的大样本中，急性运动引起循环代谢组的广泛变化。代谢变化确定心脏代谢健康、CVD和长期结果的核心途径。这些发现提供了人类对急性运动的代谢反应的详细地图，并确定了运动对心脏代谢有益影响的潜在机制，以供未来研究。
While regular exercise exposure is associated with lower risk of cardiovascular disease (CVD) and mortality, mechanisms of exercise-mediated health benefits remain less clear. We used metabolite profiling before and after acute exercise to delineate the metabolic architecture of exercise response patterns in humans. Cardiopulmonary exercise testing (CPET) and metabolite profiling was performed on Framingham Heart Study (FHS) participants (age 53±8 years, 63% women) with blood drawn at rest (n=471) and at peak exercise (n=411). We observed changes in circulating levels for 502 of 588 measured metabolites from rest to peak exercise (exercise duration 11.9±2.1 minutes) at a 5% false discovery rate (FDR). Changes included reductions in metabolites implicated in insulin resistance (glutamate −29%, P=1.5x10−55, dimethylguanidinovaleric acid −18%, P=5.8x10−18), and increases in metabolites associated with lipolysis (1-methylnicotinamide, +33%, P=6.1x10−67), nitric oxide bioavailability (arginine/ornithine + citrulline, +29%, P=2.8x10−169), and adipose browning (12,13-dihydroxy-9Z-octadecenoic acid +26%, P=7.4x10−38), among other pathways relevant to cardiometabolic risk. We assayed 177 metabolites in a separate FHS replication sample (n=783, age 54±8 years, 51% women) and observed concordant changes in 164 metabolites (92.6%) at 5% FDR. Exercise-induced metabolite changes were variably related to the amount of exercise performed (peak workload), sex, and body mass index (BMI). There was attenuation of favorable excursions in some metabolites in individuals with higher BMI and greater excursions in select cardioprotective metabolites in women despite less exercise performed. Distinct pre-exercise metabolite levels were associated with different physiologic dimensions of fitness (e.g., ventilatory efficiency, exercise blood pressure, peak VO2). We identified four metabolite signatures of exercise response patterns that were then analyzed in a separate cohort (Framingham Offspring Study; n=2045, age 55±10 years, 51% women), two of which were associated with overall mortality over median follow-up of 23.1 years (P≤0.003 for both). In a large sample of community-dwelling individuals, acute exercise elicits widespread changes in the circulating metabolome. Metabolic changes identify pathways central to cardiometabolic health, CVD, and long-term outcome. These findings provide a detailed map of the metabolic response to acute exercise in humans and identify potential mechanisms responsible for the beneficial cardiometabolic effects of exercise for future study.