Abstract:
Elevated circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are associated with obesity and type 2 diabetes (T2D). Reducing circulatory BCAAs by dietary restriction was suggested to mitigate these risks in rodent models, but this is a challenging paradigm to deliver in humans. We aimed to design and assess the feasibility of a diet aimed at reducing circulating BCAA concentrations in humans, while maintaining energy balance and overall energy/protein intake. Twelve healthy individuals were assigned to either a 7-day BCAA-restricted diet or a 7-day control diet. Diets were iso-nitrogenous and iso-caloric, with only BCAA levels differing between the two. The BCAA-restricted diet significantly reduced circulating BCAA concentrations by ~50% i.e., baseline 437 ± 60 to 217 ± 40 µmol/L (p < 0.005). Individually, both valine (245 ± 33 to 105 ± 23 µmol/L; p < 0.0001), and leucine (130 ± 20 to 75 ± 13 µmol/L; p < 0.05), decreased significantly in response to the BCAA-restricted diet. The BCAA-restricted diet marginally lowered Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels: baseline 1.5 ± 0.2 to 1.0 ± 0.1; (p = 0.096). We successfully lowered circulating BCAAs by 50% while maintaining iso-nitrogenous, iso-caloric dietary intakes, and while meeting the recommended daily allowances (RDA) for protein requirements. The present pilot study represents a novel dietary means by which to reduce BCAA, and as such, provides a blueprint for a potential dietary therapeutic in obesity/diabetes.
摘要:
升高的循环支链氨基酸(BCAAs;异亮氨酸,亮氨酸,和缬氨酸)与肥胖和2型糖尿病(T2D)有关。在啮齿动物模型中,建议通过饮食限制减少循环BCAA来减轻这些风险。但这对人类来说是一个具有挑战性的范例。我们旨在设计和评估旨在降低人体循环BCAA浓度的饮食的可行性,同时保持能量平衡和整体能量/蛋白质摄入量。12名健康个体被分配到7天BCAA限制饮食或7天控制饮食。饮食是等氮和等热量的,两者之间只有BCAA水平不同。BCAA限制饮食显着降低循环BCAA浓度约50%,即基线437±60至217±40µmol/L(p<0.005)。个别地,两种缬氨酸(245±33至105±23µmol/L;p<0.0001),和亮氨酸(130±20至75±13µmol/L;p<0.05),对BCAA限制饮食的反应显着降低。BCAA限制的饮食略微降低了胰岛素抵抗的稳态模型评估(HOMA-IR)水平:基线1.5±0.2至1.0±0.1;(p=0.096)。我们成功地将循环BCAA降低了50%,同时保持了等氮,等热量膳食摄入量,同时满足蛋白质需求的建议每日配额(RDA)。本试点研究代表了一种新的饮食手段,通过它来减少BCAA,因此,为肥胖/糖尿病的潜在饮食治疗提供了蓝图。