Abstract：
We recently demonstrated that acute oral ketone monoester intake induces a stimulation of postprandial myofibrillar protein synthesis rates comparable to that elicited following the ingestion of 10 g whey protein or their coingestion. The present investigation aimed to determine the acute effects of ingesting a ketone monoester, whey protein, or their coingestion on mechanistic target of rapamycin (mTOR)-related protein-protein colocalization and intracellular trafficking in human skeletal muscle. In a randomized, double-blind, parallel group design, 36 healthy recreationally active young males (age: 24.2 ± 4.1 yr) ingested either: 1) 0.36 g·kg-1 bodyweight of the ketone monoester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (KET), 2) 10 g whey protein (PRO), or 3) the combination of both (KET + PRO). Muscle biopsies were obtained in the overnight postabsorptive state (basal conditions), and at 120 and 300 min in the postprandial period for immunofluorescence assessment of protein translocation and colocalization of mTOR-related signaling molecules. All treatments resulted in a significant (Interaction: P < 0.0001) decrease in tuberous sclerosis complex 2 (TSC2)-Ras homolog enriched in brain (Rheb) colocalization at 120 min versus basal; however, the decrease was sustained at 300 min versus basal (P < 0.0001) only in KET + PRO. PRO and KET + PRO increased (Interaction: P < 0.0001) mTOR-Rheb colocalization at 120 min versus basal; however, KET + PRO resulted in a sustained increase in mTOR-Rheb colocalization at 300 min that was greater than KET and PRO. Treatment intake increased mTOR-wheat germ agglutinin (WGA) colocalization at 120 and 300 min (Time: P = 0.0031), suggesting translocation toward the fiber periphery. These findings demonstrate that ketone monoester intake can influence the spatial mechanisms involved in the regulation of mTORC1 in human skeletal muscle.NEW & NOTEWORTHY We explored the effects of a ketone monoester (KET), whey protein (PRO), or their coingestion (KET + PRO) on mTOR-related protein-protein colocalization and intracellular trafficking in human muscle. All treatments decreased TSC2-Rheb colocalization at 120 minutes; however, KET + PRO sustained the decrease at 300 min. Only PRO and KET + PRO increased mTOR-Rheb colocalization; however, the increase at 300 min was greater in KET + PRO. Treatment intake increased mTOR-WGA colocalization, suggesting translocation to the fiber periphery. Ketone bodies influence the spatial regulation of mTOR.
摘要：
我们最近证明，急性口服酮单酯摄入会刺激餐后肌原纤维蛋白合成速率，与摄入10g乳清蛋白或其共同摄入后引起的刺激相当。本研究旨在确定摄入酮单酯的急性影响，乳清蛋白,或它们对mTOR相关蛋白质-蛋白质共定位和细胞内运输的共同摄取在人类骨骼肌中。在一个随机的，双盲,并行组设计，36名健康的娱乐性活跃的年轻男性（年龄：24.2±4.1岁）摄入以下任一者：1）酮单酯（R）-3-羟基丁基（R）-3-羟基丁酸酯（KET）的0.36g•kg-1体重，2）10克乳清蛋白（PRO），或3)两者的组合(KET+PRO)。在过夜吸收后状态（基础条件）下获得肌肉活检，在餐后120-和300-分钟，用于免疫荧光评估mTOR相关信号分子的蛋白易位和共定位。与120分钟相比，所有治疗均导致富含脑（Rheb）共定位的结节性硬化症2（TSC2）-Ras同系物显着降低（相互作用：P<0.0001）基底；然而，下降持续300分钟与基底（P<0.0001）仅在KET+PRO中。PRO和KETPRO增加（相互作用：P<0.0001）mTOR-Rheb在120分钟与基底；然而，KET+PRO导致mTOR-Rheb共定位在300分钟时持续增加,其大于KET和PRO。处理摄入量增加mTOR-小麦胚芽凝集素（WGA）共定位在120和300分钟（时间：P=0.0031），提示向纤维外围易位。这些发现表明，酮单酯的摄入可以影响人骨骼肌中mTORC1调节的空间机制。
