慢性胎儿亮氨酸输注增加晚期妊娠胎儿羊亮氨酸氧化率，但不增加蛋白质合成率。
Chronic Fetal Leucine Infusion Increases Rate of Leucine Oxidation but Not of Protein Synthesis in Late Gestation Fetal Sheep.
机构信息
Department of Pediatrics, University of Colorado School of Medicine, Perinatal Research Center, Aurora, Colorado, USA.
Department of Pediatrics, University of Colorado School of Medicine, Perinatal Research Center, Aurora, Colorado, USA.
出版信息
J Nutr. 2023 Feb;153(2):493-504. doi: 10.1016/j.tjnut.2022.12.027. Epub 2022 Dec 30.
BACKGROUND
Leucine increases protein synthesis rates in postnatal animals and adults. Whether supplemental leucine has similar effects in the fetus has not been determined.
OBJECTIVE
To determine the effect of a chronic leucine infusion on whole-body leucine oxidation and protein metabolic rates, muscle mass, and regulators of muscle protein synthesis in late gestation fetal sheep.
METHODS
Catheterized fetal sheep at ∼126 d of gestation (term = 147 d) received infusions of saline (CON, n = 11) or leucine (LEU; n = 9) adjusted to increase fetal plasma leucine concentrations by 50%-100% for 9 d. Umbilical substrate net uptake rates and protein metabolic rates were determined using a 1-C leucine tracer. Myofiber myosin heavy chain (MHC) type and area, expression of amino acid transporters, and abundance of protein synthesis regulators were measured in fetal skeletal muscle. Groups were compared using unpaired t tests.
RESULTS
Plasma leucine concentrations were 75% higher in LEU fetuses compared with CON by the end of the infusion period (P < 0.0001). Umbilical blood flow and uptake rates of most amino acids, lactate, and oxygen were similar between groups. Fetal whole-body leucine oxidation was 90% higher in LEU (P < 0.0005) but protein synthesis and breakdown rates were similar. Fetal and muscle weights and myofiber areas were similar between groups, however, there were fewer MHC type IIa fibers (P < 0.05), greater mRNA expression levels of amino acid transporters (P < 0.01), and a higher abundance of signaling proteins that regulate protein synthesis (P < 0.05) in muscle from LEU fetuses.
CONCLUSIONS
A direct leucine infusion for 9 d in late gestation fetal sheep does not increase protein synthesis rates but results in higher leucine oxidation rates and fewer glycolytic myofibers. Increasing leucine concentrations in the fetus stimulates its own oxidation but also increases amino acid transporter expression and primes protein synthetic pathways in skeletal muscle.
背景
亮氨酸能提高新生动物和成年动物的蛋白质合成速率。补充亮氨酸是否对胎儿有类似的影响尚未确定。
目的
确定在妊娠晚期胎儿羊中慢性亮氨酸输注对全身亮氨酸氧化和蛋白质代谢率、肌肉质量以及肌肉蛋白合成调节剂的影响。
方法
在妊娠约 126 天（足月= 147 天）的胎儿羊上插入导管，接受生理盐水（CON，n = 11）或亮氨酸（LEU；n = 9）输注，以将胎儿血浆亮氨酸浓度提高 50%-100%，持续 9 天。使用 1-C 亮氨酸示踪剂测定脐基质净摄取率和蛋白质代谢率。测量胎儿骨骼肌中肌球蛋白重链（MHC）型和面积、氨基酸转运体的表达以及蛋白质合成调节剂的丰度。使用未配对 t 检验比较组间差异。
结果
输注期末，LEU 胎儿的血浆亮氨酸浓度比 CON 组高 75%（P < 0.0001）。两组间的脐血流和大多数氨基酸、乳酸和氧的摄取率相似。LEU 组胎儿全身亮氨酸氧化率高 90%（P < 0.0005），但蛋白质合成和分解率相似。两组胎儿和肌肉重量以及肌纤维面积相似，但 LEU 胎儿的 MHC Ⅱa 型纤维较少（P < 0.05），氨基酸转运体的 mRNA 表达水平较高（P < 0.01），以及调节蛋白质合成的信号蛋白丰度较高（P < 0.05）。
结论
在妊娠晚期胎儿羊中进行 9 天的直接亮氨酸输注不会增加蛋白质合成率，但会导致亮氨酸氧化率增加和糖酵解肌纤维减少。胎儿亮氨酸浓度增加刺激其自身氧化，同时增加氨基酸转运体的表达，并使骨骼肌中的蛋白质合成途径处于激活状态。
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