Department of Physiology, Faculty of Medicine, University of Alexandria, Alexandria, Egypt.
Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.
J Nutr. 2018 Jul 1;148(7):1073-1080. doi: 10.1093/jn/nxy062.
Plasma concentrations of branched-chain amino acids (BCAAs) and the sulfur-containing amino acid cysteine are associated with obesity and insulin resistance. BCAAs predict future diabetes.
We investigated amino acid changes during food overconsumption.
Forty healthy men and women with a body mass index (mean ± SEM) of 25.6 ± 0.6 were overfed by 1250 kcal/d for 28 d, increasing consumption of all macronutrients. Insulin sensitivity and body composition were assessed at baseline (day 0) and day 28. Fasting serum amino acids were measured at days 0, 3, and 28. Linear mixed-effects models evaluated the effect of time in the total group and separately in those with low and high body fat gain (below compared with at or above median fat gain, 1.95 kg). At days 0 and 28, insulin-induced suppression of serum amino acids during a hyperinsulinemic-euglycemic clamp test and, in a subset (n = 20), adipose tissue mRNA expression of selected amino acid metabolizing enzymes were assessed.
Weight increased by 2.8 kg. High fat gainers gained 2.6 kg fat mass compared with 1.1 kg in low fat gainers. Valine and isoleucine increased at day 3 (+17% and +22%, respectively; P ≤ 0.002) and remained elevated at day 28, despite a decline in valine (P = 0.019) from day 3 values. Methionine, cystathionine, and taurine were unaffected. Serum total cysteine (tCys) transiently increased at day 3 (+11%; P = 0.022) only in high fat gainers (P-interaction = 0.043), in whom the cysteine catabolic enzyme cysteine dioxygenase (CDO1) was induced (+26%; P = 0.025) in adipose tissue (P-interaction = 0.045). Overconsumption did not alter adipose tissue mRNA expression of the BCAA-metabolizing enzymes branched-chain keto acid dehydrogenase E1α polypeptide (BCKDHA) or branched-chain amino transferase 1 (BCAT1). In the total population at day 0, insulin infusion decreased all serum amino acids (-11% to -47%; P < 0.01), except for homocysteine and tCys, which were unchanged, and glutathione, which was increased by 54%. At day 28, insulin increased tCys (+8%), and the insulin-induced suppression of taurine and phenylalanine observed at day 0, but not that of BCAAs, was significantly impaired.
These findings highlight the role of nutrient oversupply in increasing fasting BCAA concentrations in healthy adults. The link between cysteine availability, CDO1 expression, and fat gain deserves investigation. This trial was registered at www.clinicaltrials.gov as NCT00562393.
血浆支链氨基酸（BCAA）和含硫氨基酸半胱氨酸的浓度与肥胖和胰岛素抵抗有关。BCAA 可预测未来的糖尿病。
我们研究了食物摄入过多时氨基酸的变化。
40 名身体质量指数（BMI）（均值±SEM）为 25.6±0.6 的健康男女通过每天 1250 千卡的热量摄入过度进食 28 天，增加了所有宏量营养素的消耗。在基线（第 0 天）和第 28 天评估胰岛素敏感性和身体成分。在第 0、3 和 28 天测量空腹血清氨基酸。线性混合效应模型评估了总组以及低体脂增加（与体脂增加中位数相比低于或高于中位数，1.95 公斤）和高体脂增加组的时间影响。在第 0 天和第 28 天，通过高胰岛素-正常血糖钳夹试验评估了胰岛素对血清氨基酸的抑制作用，并在亚组（n=20）中评估了选定氨基酸代谢酶的脂肪组织 mRNA 表达。
体重增加了 2.8 公斤。高体脂增加者的体脂增加了 2.6 公斤，而低体脂增加者的体脂增加了 1.1 公斤。缬氨酸和异亮氨酸在第 3 天分别增加了 17%和 22%（P≤0.002），并在第 28 天仍保持升高，尽管第 3 天的缬氨酸下降（P=0.019）。蛋氨酸、胱硫醚和牛磺酸没有变化。血清总半胱氨酸（tCys）仅在第 3 天（增加 11%；P=0.022）在高体脂增加者中短暂增加（P 交互=0.043），在这些高体脂增加者中，半胱氨酸分解酶胱氨酸双加氧酶（CDO1）被诱导（增加 26%；P=0.025）在脂肪组织中（P 交互=0.045）。过度进食并没有改变 BCAA 代谢酶支链酮酸脱氢酶 E1α 多肽（BCKDHA）或支链氨基酸转移酶 1（BCAT1）在脂肪组织中的 mRNA 表达。在第 0 天的总人群中，胰岛素输注降低了所有血清氨基酸（-11%至-47%；P<0.01），除了同型半胱氨酸和 tCys 不变，谷胱甘肽增加了 54%。在第 28 天，胰岛素增加了 tCys（增加 8%），并且第 0 天观察到的胰岛素诱导的牛磺酸和苯丙氨酸的抑制作用，但不是 BCAAs 的抑制作用显著受损。
这些发现强调了营养物质过剩在增加健康成年人空腹 BCAA 浓度方面的作用。半胱氨酸可用性、CDO1 表达和体脂增加之间的联系值得进一步研究。该试验在 www.clinicaltrials.gov 上注册为 NCT00562393。
