Abstract：
OBJECTIVE: Trimethylamine-N-oxide (TMAO) is a gut-derived metabolite associated with cardiovascular disease (CVD). In preclinical and observational studies, resveratrol and exercise training have been suggested as potential strategies to reduce the systemic levels of TMAO. However, evidence from experimental studies in humans remains unknown. This project examined the dose-dependent effects of a combined resveratrol intervention with exercise training on circulating TMAO and other related metabolite signatures in older adults with high CVD risk.
METHODS: Forty-one older adults [mean (±SD) age of 72.1 (6.8) years] participated in a 12-week supervised center-based, multi-component exercise training intervention [2×/week; 80 min/session] and were randomized to one of two resveratrol dosages [Low: 500 vs. High:1000 mg/day] or a cellulose-based placebo. Serum/plasma were collected at baseline and post-intervention and evaluated for TMAO and associated analytes.
RESULTS: After the 12-week intervention, TMAO concentration increased over time, regardless of treatment [mean (±SD) Placebo: 11262 (±3970); Low:13252 (±1193); High: 12661(±3359) AUC; p = 0.04]. Each resveratrol dose produced different changes in metabolite signatures. Low dose resveratrol upregulated metabolites associated with bile acids biosynthesis (i.e., glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycocholic acid). High dose resveratrol modulated metabolites enriched for glycolysis, and pyruvate, propanoate, β-alanine, and tryptophan metabolism. Different communities tightly correlated to TMAO and resveratrol metabolites were associated with the lipid and vascular inflammatory clinical markers [|r| > 0.4, p < 0.05].
CONCLUSIONS: These findings suggest a distinct dose-dependent adaptation response to resveratrol supplementation on circulating metabolite signatures but not on TMAO among high-risk CVD older adults when combined with an exercise training intervention.
METHODS: Forty-one older adults [mean (±SD) age of 72.1 (6.8) years] participated in a 12-week supervised center-based, multi-component exercise training intervention [2×/week; 80 min/session] and were randomized to one of two resveratrol dosages [Low: 500 vs. High:1000 mg/day] or a cellulose-based placebo. Serum/plasma were collected at baseline and post-intervention and evaluated for TMAO and associated analytes.
RESULTS: After the 12-week intervention, TMAO concentration increased over time, regardless of treatment [mean (±SD) Placebo: 11262 (±3970); Low:13252 (±1193); High: 12661(±3359) AUC; p = 0.04]. Each resveratrol dose produced different changes in metabolite signatures. Low dose resveratrol upregulated metabolites associated with bile acids biosynthesis (i.e., glycochenodeoxycholic acid, glycoursodeoxycholic acid, and glycocholic acid). High dose resveratrol modulated metabolites enriched for glycolysis, and pyruvate, propanoate, β-alanine, and tryptophan metabolism. Different communities tightly correlated to TMAO and resveratrol metabolites were associated with the lipid and vascular inflammatory clinical markers [|r| > 0.4, p < 0.05].
CONCLUSIONS: These findings suggest a distinct dose-dependent adaptation response to resveratrol supplementation on circulating metabolite signatures but not on TMAO among high-risk CVD older adults when combined with an exercise training intervention.
摘要：
目的：三甲胺-N-氧化物（TMAO）是一种与心血管疾病（CVD）相关的肠道代谢产物。在临床前和观察性研究中，白藜芦醇和运动训练已被认为是降低TMAO系统水平的潜在策略。然而,人类实验研究的证据仍然未知。该项目研究了白藜芦醇干预与运动训练相结合对心血管疾病风险高的老年人循环TMAO和其他相关代谢物特征的剂量依赖性影响。
方法：41名老年人[平均（±SD）年龄为72.1（6.8）岁]参加了为期12周的中心监督，多组分运动训练干预[2×/周；80分钟/次]，并随机分配至两种白藜芦醇剂量之一[低：500vs.高：1000毫克/天]或基于纤维素的安慰剂。在基线和干预后收集血清/血浆并评估TMAO和相关分析物。
结果：经过12周的干预后，TMAO浓度随时间增加,无论治疗[平均值(±SD)安慰剂:11262(±3970);低:13252(±1193);高:12661(±3359)AUC;p=0.04]。每种白藜芦醇剂量在代谢物特征中产生不同的变化。低剂量白藜芦醇上调与胆汁酸生物合成相关的代谢物(即，糖脱氧胆酸，甘草脱氧胆酸，和甘胆酸）。高剂量白藜芦醇调节代谢产物富含糖酵解，还有丙酮酸,丙酸盐,β-丙氨酸,和色氨酸代谢.不同群落与TMAO密切相关,白藜芦醇代谢产物与脂质和血管炎症临床标志物相关[|r|>0.4,p<0.05]。
结论：这些研究结果表明，在高风险CVD老年人中，与运动训练干预相结合时，白藜芦醇补充剂对循环代谢物特征有明显的剂量依赖性适应反应，而对TMAO则没有。
方法：41名老年人[平均（±SD）年龄为72.1（6.8）岁]参加了为期12周的中心监督，多组分运动训练干预[2×/周；80分钟/次]，并随机分配至两种白藜芦醇剂量之一[低：500vs.高：1000毫克/天]或基于纤维素的安慰剂。在基线和干预后收集血清/血浆并评估TMAO和相关分析物。
结果：经过12周的干预后，TMAO浓度随时间增加,无论治疗[平均值(±SD)安慰剂:11262(±3970);低:13252(±1193);高:12661(±3359)AUC;p=0.04]。每种白藜芦醇剂量在代谢物特征中产生不同的变化。低剂量白藜芦醇上调与胆汁酸生物合成相关的代谢物(即，糖脱氧胆酸，甘草脱氧胆酸，和甘胆酸）。高剂量白藜芦醇调节代谢产物富含糖酵解，还有丙酮酸,丙酸盐,β-丙氨酸,和色氨酸代谢.不同群落与TMAO密切相关,白藜芦醇代谢产物与脂质和血管炎症临床标志物相关[|r|>0.4,p<0.05]。
结论：这些研究结果表明，在高风险CVD老年人中，与运动训练干预相结合时，白藜芦醇补充剂对循环代谢物特征有明显的剂量依赖性适应反应，而对TMAO则没有。
