Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients.

Dysregulated Handling of Dietary Protein and Muscle Protein Synthesis After Mixed-Meal Ingestion in Maintenance Hemodialysis Patients.
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DOI:
10.1016/j.ekir.2018.08.001
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发表时间:
2018-11
影响因子:
6
通讯作者:
Burd NA
Burd NA
中科院分区:
医学2区
文献类型:
--
作者:
van Vliet S;Skinner SK;Beals JW;Pagni BA;Fang HY;Ulanov AV;Li Z;Paluska SA;Mazzulla M;West DWD;Moore DR;Wilund KR;Burd NA

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在接受维持性血液透析(MHD)治疗的肾衰竭患者中,骨骼肌丢失是常见的。建议定期摄入富含蛋白质的膳食,以帮助抵消MHD患者的肌肉蛋白质损失,但对这种策略的合成代谢潜力知之甚少。8例MHD患者(年龄:56 ± 5岁;体重指数[BMI]:32 ± 2 kg/m2)和8例非尿毒症对照受试者(年龄:50 ± 2岁; BMI:31 ± 1 kg/m2)接受预充连续L-[环-2H5]苯丙氨酸和L-[1- 13 C]亮氨酸输注,并在非透析日进行血液和肌肉活检采样。参与者食用混合餐(546千卡; 20克蛋白质,59克碳水化合物,26克脂肪),蛋白质以L-[5,5,5 - 2 H3]亮氨酸标记的鸡蛋提供。MHD患者(41 ± 5%)与对照受试者(61 ± 4%; P = 0.03)相比,循环膳食氨基酸利用率降低。与对照组相比,MHD患者基底肌caspase-3蛋白含量升高(P = 0.03),大中性氨基酸转运蛋白1(LAT 1)蛋白含量降低(P = 0.02)。MHD患者的基础肌蛋白合成(MPS)(0.030 ± 0.005%/h)是对照组(0.014 ± 0.003%/h)的102倍(P = 0.01)。MHD患者的进食未能增加MPS(相对于基础值的绝对变化:0.0003 ± 0.007%/h),但在对照组中刺激了MPS(0.009 ± 0.002%/h; P = 0.004)。MHD患者表现出对膳食摄入的肌肉合成代谢抵抗。MHD患者餐后MPS反应减弱可能与基础MPS升高有关,导致混合餐摄入后刺激性上限效应和/或血浆膳食氨基酸利用率降低。
Skeletal muscle loss is common in patients with renal failure who receive maintenance hemodialysis (MHD) therapy. Regular ingestion of protein-rich meals are recommended to help offset muscle protein loss in MHD patients, but little is known about the anabolic potential of this strategy. Eight MHD patients (age: 56 ± 5 years; body mass index [BMI]: 32 ± 2 kg/m2) and 8 nonuremic control subjects (age: 50 ± 2 years: BMI: 31 ± 1 kg/m2) received primed continuous L-[ring-2H5]phenylalanine and L-[1-13C]leucine infusions with blood and muscle biopsy sampling on a nondialysis day. Participants consumed a mixed meal (546 kcal; 20-g protein, 59-g carbohydrates, 26-g fat) with protein provided as L-[5,5,5-2H3]leucine-labeled eggs. Circulating dietary amino acid availability was reduced in MHD patients (41 ± 5%) versus control subjects (61 ± 4%; P = 0.03). Basal muscle caspase-3 protein content was elevated (P = 0.03) and large neutral amino acid transporter 1 (LAT1) protein content was reduced (P = 0.02) in MHD patients versus control subjects. Basal muscle protein synthesis (MPS) was ∼2-fold higher in MHD patients (0.030 ± 0.005%/h) versus control subjects (0.014 ± 0.003%/h) (P = 0.01). Meal ingestion failed to increase MPS in MHD patients (absolute change from basal: 0.0003 ± 0.007%/h), but stimulated MPS in control subjects (0.009 ± 0.002%/h; P = 0.004). MHD patients demonstrated muscle anabolic resistance to meal ingestion. This blunted postprandial MPS response in MHD patients might be related to high basal MPS, which results in a stimulatory ceiling effect and/or reduced plasma dietary amino acid availability after mixed-meal ingestion.
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