Lifestyle, branched-chain amino acids, and cardiovascular risk factors: a randomized trial

摘要 心血管疾病（CVD）是全球过早死亡的主要原因， 胰岛素抵抗和2型糖尿病的发病率正在增加。因此，更有效的预防 迫切需要采取干预措施改善心脏代谢健康。循环支链氨基酸 BCAA是2型糖尿病和CVD的强预测因子。此外，实验和遗传研究 表明BCAA过量具有不利心脏代谢作用。因此，BCAA水平可能是新的目标， 预防性干预。此外，个人的BCAA水平可以为个性化干预提供信息。 越来越多的证据表明，饮食结构、体育活动和减肥可以降低血浆BCAA 通过影响饮食供应，肠道微生物群的生产或BCAA的催化剂水平。然而，证据显示， 生活方式因素对BCAA水平的影响主要基于小型实验研究和交叉研究， 分段研究。大型试验和纵向研究对于确定生活方式是否 暴露会严重影响BCAA水平。此外，研究对健康的影响， 支链氨基酸水平主要集中在支链氨基酸水平对葡萄糖代谢的影响，但对葡萄糖代谢的不利影响。 其他CVD危险因素如炎症、血压和血脂异常是合理的。英超 这项研究是一项关于行为生活方式干预对CVD危险因素影响的随机试验， 基于访谈和生物测量的饮食和体育活动信息。我们将测量 使用靶向定量NMR代谢组学对729例血清样本中的血清BCAA和其他代谢物进行分析， 参与者在基线和六个月的生活方式干预后。我们的具体目标如下：1）。到 评估随机生活方式干预对循环BCAA水平的影响， 个月我们将评估“既定生活方式干预”的效果，包括减肥和 增加体力活动，以及增加咨询以改善饮食的干预效果 与对照组相比，2）。评估特定的饮食因素，体力活动， 肥胖的变化与BCAA的变化有关。我们将检查身体活动，健康， 蛋白质和支链氨基酸的摄入量，以及健康的植物性饮食模式。3）。为了评估是否有变化， 支链氨基酸水平影响心脏代谢危险因素，包括血脂谱，血压， 炎症和胰岛素敏感性的标志物。我们还将估计以下因素的影响比例： 生活方式的改变对心血管危险因素的影响可以通过BCAA水平的降低来解释。我们的研究结果可能 告知饮食和生活方式的建议，考虑对BCAA水平的影响。

Abstract Cardiovascular diseases (CVD) are the primary cause of premature death worldwide, and risk factors such as insulin resistance and type 2 diabetes are increasing in prevalence. Therefore, more effective preventive interventions to improve cardiometabolic health are urgently needed. Circulating branched-chain amino acids (BCAA) are strong predictors of type 2 diabetes and CVD. Furthermore, experimental and genetic studies indicate that BCAA overload has adverse cardiometabolic effects. Thus, BCAA levels may be novel targets for preventive interventions. In addition, BCAA levels of individuals may inform personalized interventions. Evidence is accumulating that diet composition, physical activity, and weight loss can reduce plasma BCAA levels by affecting the dietary supply, gut microbiota production, or catabolism of BCAA. However, evidence on the impact of lifestyle factors on BCAA levels is mainly based on small experimental studies and cross- sectional studies. Larger trials and longitudinal studies are crucial to determine whether lifestyle exposures can substantially affect BCAA levels. Furthermore, research on the health consequences of BCAA levels has focused chiefly on the impact of BCAA levels on glucose metabolism, but adverse effects on other CVD risk factors such as inflammation, blood pressure, and dyslipidemia are plausible. The PREMIER study is a randomized trial of the impact of behavioral lifestyle interventions on CVD risk factors with detailed information on diet and physical activity based on interviews and biological measurements. We will measure serum BCAA and other metabolites using targeted quantitative NMR metabolomics in serum samples of 729 participants at baseline and after six months of lifestyle interventions. Our specific aims are as follows: 1). To assess the impact of the randomized lifestyle interventions on circulating BCAA levels over six months. We will evaluate the effect of the ‘established lifestyle intervention,’ including weight loss and increases in physical activity, and the effect of the intervention with added counseling to improve dietary patterns as compared with the control arm. 2). To evaluate specific dietary factors, physical activity, and changes in adiposity in relation to BCAA changes. We will examine changes in physical activity, fitness, protein and BCAA intakes, and healthy plant-based dietary patterns. 3). To evaluate whether changes in BCAA levels affect cardio-metabolic risk factors, including blood lipid profiles, blood pressure, and markers of inflammation and insulin sensitivity. We will also estimate the proportion of the effects of lifestyle changes on cardiovascular risk factors explained by reductions in BCAA levels. Our findings may inform dietary and lifestyle recommendations that consider the impact on BCAA levels.