Giesbertz Pieter, Daniel Hannelore
Nutritional Physiology, Technische Universität München, Germany.
Curr Opin Clin Nutr Metab Care. 2016 Jan;19(1):48-54. doi: 10.1097/MCO.0000000000000235.
Numerous human studies have consistently demonstrated that concentrations of branched-chain amino acids (BCAAs) in plasma and urine are associated with insulin resistance and have the quality to predict diabetes development. However, it is not known how altered BCAA levels link to insulin action and diabetes. This review addresses some recent findings in BCAA metabolism and discusses their role as reporter molecules of insulin sensitivity and diabetes and their possible contribution to disease progression.
Changes in plasma and urine levels result mainly from altered metabolism in tissues and recent studies have thus focused on organ-specific changes in BCAA handling using animal models and human tissue samples. A decreased mitochondrial oxidation has been demonstrated in peripheral tissues and that was shown to be associated with an increased inflammatory tone and changes in adipokine levels (adiponectin and leptin). These changes appear already before insulin resistance is established. Key findings demonstrating the discordance between changes in BCAA and insulin resistance are derived from studies using insulin sensitizers and from data collected in patients undergoing Roux-en-Y bypass bariatric surgery. Intermediates derived from BCAA breakdown rather than BCAA itself were recently proposed to contribute to the development of insulin resistance and studies now explore the biomarker qualities of these metabolites.
Understanding the mechanisms and putative causalities in the alterations in BCAA levels as found in obesity, metabolic syndrome and diabetes is crucial for any intervention options but also for the use of BCAA and derivatives as biomarkers in clinical routine.
众多人体研究一致表明，血浆和尿液中支链氨基酸（BCAAs）的浓度与胰岛素抵抗相关，且具备预测糖尿病发生的能力。然而，尚不清楚BCAAs水平的改变如何与胰岛素作用及糖尿病相联系。本综述阐述了BCAAs代谢的一些最新发现，并讨论了它们作为胰岛素敏感性和糖尿病的报告分子的作用，以及它们对疾病进展的可能影响。
血浆和尿液水平的变化主要源于组织代谢的改变，因此近期研究利用动物模型和人体组织样本，聚焦于BCAAs处理过程中的器官特异性变化。已证实在外周组织中线粒体氧化减少，且这与炎症反应增强及脂肪因子水平（脂联素和瘦素）变化相关。这些变化在胰岛素抵抗形成之前就已出现。证明BCAAs变化与胰岛素抵抗不一致的关键发现，来自使用胰岛素增敏剂的研究以及接受Roux-en-Y胃旁路减肥手术患者收集的数据。最近有人提出，BCAAs分解产生的中间体而非BCAAs本身，会导致胰岛素抵抗的发生，目前的研究正在探索这些代谢产物作为生物标志物的特性。
了解肥胖、代谢综合征和糖尿病中BCAAs水平改变的机制及假定因果关系，对于任何干预措施都至关重要，对于在临床常规中使用BCAAs及其衍生物作为生物标志物也同样重要。
