Enteral β-hydroxy-β-methylbutyrate supplementation increases protein synthesis in skeletal muscle of neonatal pigs
Enteral β-hydroxy-β-methylbutyrate supplementation increases protein synthesis in skeletal muscle of neonatal pigs
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DOI：
10.1152/ajpendo.00520.2015
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发表时间：
2016-06-01
影响因子：
5.1
通讯作者：
Davis, Teresa A.
中科院分区：
文献类型：
--
作者：
Kao, Michelle;Columbus, Daniel A.;Davis, Teresa A.
由于无法获得足够的蛋白质摄入量，许多低出生体重儿面临发育不良的风险。给予氨基酸亮氨酸刺激新生儿骨骼肌中蛋白质的合成。为了确定肠内添加亮氨酸代谢物β-羟基-β-甲基丁酸酯(HMB)对蛋白质合成和翻译起始及降解途径的调节作用，对隔夜禁食的新生仔猪进行了研究，分别饲喂低蛋白(LP)、高蛋白(HP)和添加4(HMB4)、40(HMB40)或80(HMB80)mU HMB的低蛋白(LP)、高蛋白(HP)或添加80(HMB80)mU HMB的日粮。通过背最长肌和空肠隐窝细胞中BrdU的核掺入来评估细胞复制。HMB80组和HP组LD、腓肠肌、菱形肌和横隔肌、肺和脑的蛋白质合成率高于LP组和F组，HMB40组脑蛋白质合成率高于LP组和F组。HMB80和HP组LD、腓肠肌和菱形肌中eIF4E.eIF4G复合体的形成以及S6K1和4E-BP1的磷酸化程度高于LP组和F组。EIF2α和eEF2的磷酸化以及SNAT2、LAT1、MuRF1、阿托金-1和LC3-II的表达没有变化。HMB80组和HP组LD内BrdU阳性肌核数目多于LP组和F组，空肠无差异。提示肠内补充HMB可通过促进蛋白质合成和卫星细胞增殖来促进新生儿骨骼肌蛋白质合成代谢。
Many low-birth weight infants are at risk for poor growth due to an inability to achieve adequate protein intake. Administration of the amino acid leucine stimulates protein synthesis in skeletal muscle of neonates. To determine the effects of enteral supplementation of the leucine metabolite beta-hydroxy-beta-methylbutyrate (HMB) on protein synthesis and the regulation of translation initiation and degradation pathways, overnight-fasted neonatal pigs were studied immediately (F) or fed one of five diets for 24 h: low-protein (LP), high-protein (HP), or LP diet supplemented with 4 (HMB4), 40 (HMB40), or 80 (HMB80) mu mol HMB.kg body wt(-1).day(-1). Cell replication was assessed from nuclear incorporation of BrdU in the longissimus dorsi (LD) muscle and jejunum crypt cells. Protein synthesis rates in LD, gastrocnemius, rhomboideus, and diaphragm muscles, lung, and brain were greater in HMB80 and HP and in brain were greater in HMB40 compared with LP and F groups. Formation of the eIF4E.eIF4G complex and S6K1 and 4E-BP1 phosphorylation in LD, gastrocnemius, and rhomboideus muscles were greater in HMB80 and HP than in LP and F groups. Phosphorylation of eIF2 alpha and eEF2 and expression of SNAT2, LAT1, MuRF1, atrogin-1, and LC3-II were unchanged. Numbers of BrdU-positive myonuclei in the LD were greater in HMB80 and HP than in the LP and F groups; there were no differences in jejunum. The results suggest that enteral supplementation with HMB increases skeletal muscle protein anabolism in neonates by stimulation of protein synthesis and satellite cell proliferation.