Muscle full effect after oral protein time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling
Muscle full effect after oral protein time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling
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DOI：
10.3945/ajcn.2010.29819
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发表时间：
2010-11-01
影响因子：
7.1
通讯作者：
Rennie, Michael J.
中科院分区：
文献类型：
--
作者：
Atherton, Philip J.;Etheridge, Timothy;Rennie, Michael J.
研究背景：我们以前发现，人体肌肉蛋白质合成（MPS）在输注氨基酸（AA）期间增加，尽管血浆AA浓度升高，但在恢复基线速率之前约120分钟达到峰值。目的：我们测试蛋白质餐是否引起类似的反应，以及调节信使RNA翻译的信号反应是否与MPS变化相匹配。（大约21岁）在[12-C-13（2）]亮氨酸预处理连续输注8 - 5小时期间进行研究，间歇性四头肌活检用于测定MPS和合成代谢信号传导。2 - 5小时后，受试者消耗48 g乳清蛋白。肌原纤维蛋白质合成从0.03 ± 0.003%/h增加到0.10 ± 0.01%/h，此后肌原纤维蛋白质合成恢复到基线水平，尽管血浆必需氨基酸（EAA）浓度仍然升高蛋白激酶B（PK B）的活性和真核起始因子4 G的磷酸化先于MPS的升高，核糖体蛋白激酶S6（S6 K1）和4 E结合蛋白1（4 EBP 1）磷酸化的增加与MPS反应重叠，直到90 min。尽管MPS此后降低了除PKB活性外的所有信号（反映胰岛素应答）保持升高，这与缓慢下降的血浆EAA谱相呼应。真核起始因子2 α的磷酸化仅在180分钟时增加。因此，MPS和哺乳动物雷帕霉素靶蛋白复合物1（mTORC 1）之间存在不一致性，（即S6 K1和4 EBP 1磷酸化）结论我们证实了我们先前的发现，即即使口服蛋白质推注，MPS对AA的反应也是短暂的。然而，MPS的变化仅反映了MPS上升期间mTORC 1信号的升高。Am J Clin Nutt 2010 92 1080-8
Background We previously showed that human muscle protein synthesis (MPS) increased during infusion of amino acids (AAs) and peaked at approximate to 120 min before returning to baseline rates despite elevated plasma AA concentrationsObjective We tested whether a protein meal elicited a similar response and whether signaling responses that regulate messenger RNA translation matched MPS changesDesign Eight postabsorptive healthy men (approximate to 21 y of age) were studied during 8 5 h of primed continuous infusion of [1 2-C-13(2)] leucine with intermittent quadriceps biopsies for determination of MPS and anabolic signaling After 2 5 h subjects consumed 48 g whey proteinResults At 45-90 min after oral protein bolus me in (+/- SEM) myofibrillar protein synthesis increased from 003 +/- 0 003% to 0 10 +/- 001%/h thereafter myofibrillar protein synthesis returned to baseline rates even though plasma essential AA (EAA) concentrations remained elevated (+130% at 120 mm +80% at 180 min) The activity of protein kinase B (PKB) and phosphorylation of eukaryotic initiation factor 4G preceded the rise of MPS and in creases in phosphorylation of ribosomal protein kinase S6 (S6K1) and 4E binding protein 1 (4EBP1) was superimposable with MPS responses until 90 min However, although MPS decreased thereafter all signals with the exception of PKB activity (which mirrored insulin responses) remained elevated which echoed the slowly declining plasma EAA profile The phosphorylation of eukaryotic initiation factor 2 alpha increased only at 180 min Thus, discordance existed between MPS and the mammalian target of rapamycin complex 1 (mTORC1) and signaling (ie S6K1 and 4EBP1 phosphorylation)Conclusions We confirm our previous findings that MPS responses to AAs are transient even with oral protein bolus However changes in MPS only reflect elevated mTORC1 signaling during the upswing in MPS Am J Clin Nutt 2010 92 1080-8