The muscle anabolic effect of protein ingestion during a hyperinsulinaemic euglycaemic clamp in middle‐aged women is not caused by leucine alone

Abstract

It has been suggested that leucine is primarily responsible for the increase in muscle protein synthesis (MPS) after protein ingestion because leucine uniquely activates the mTOR-p70S6K signalling cascade. We tested this hypothesis by measuring muscle p-mTOR , p-p70S6K and p-eIF2α , as well as protein turnover (by stable isotope labelled amino acid tracer infusion in conjunction with leg arteriovenous blood and muscle tissue sampling), in 28 women who consumed either 0.45 g protein kg fat-free mass (containing 0.0513 g leucine kg fat-free mass) or a control drink (n = 14) or 0.0513 g leucine kg fat-free mass or a control drink (n = 14) during a hyperinsulinaemic-euglycaemic clamp procedure (HECP). Compared to basal conditions, the HECP alone (without protein or leucine ingestion) suppressed muscle protein breakdown by ∼20% and increased p-mTOR and p-p70S6K by >50% (all P < 0.05) but had no effect on p-eIF2α and MPS. Both protein and leucine ingestion further increased p-mTOR and p-p70S6K , although only protein, and not leucine, ingestion decreased (by ∼35%) p-eIF2α and increased (by ∼100%) MPS (all P < 0.05). Accordingly, leg net protein balance changed from negative (loss) during basal conditions to equilibrium during the HECP alone and the HECP with concomitant leucine ingestion and to positive (gain) during the HECP with concomitant protein ingestion. These results provide new insights into the regulation of MPS by demonstrating that leucine and mTOR signalling alone are not responsible for the muscle anabolic effect of protein ingestion during physiological hyperinsulinaemia, most probably because they fail to signal to eIF2α to initiate translation and/or additional amino acids are needed to sustain translation.

Dietary protein, exercise, ageing and physical inactivity: interactive influences on skeletal muscle proteostasis

“…Moreover, anabolic signalling was robustly triggered when administering about 6 g BCAA (about 2⋅6 g leucine), hence leading to an increase in acute MPS response in both young muscle post-RE (79) and in older adults (80) . Conversely, it was reported that ingestion of leucine alone failed to stimulate MPS in the absence of a full EAA profile in postmenopausal (aged 50–65 years) women (81) . Bell et al reported that with 12 weeks of combined RET (about 80 % 1-repetition maximum (1-RM)) and high-intensity interval training (about 90 % maximal heart-rate), alongside consumption of a multi-ingredient supplement (consisting of 30 g whey protein, 2⋅5 g creatine, 500 IU vitamin D, 400 mg calcium and 1500 mg n -3 PUFA), myofibrillar fractional synthesis rate post-training was elevated by about 30 % and 7 % at 0–24 and 24–48 h, respectively; however, the control group demonstrated about 20 % increase in MPS compared to resting levels 24–48 h post-training (82) .…”

Anabolic Resistance of Muscle Protein Turnover Comes in Various Shapes and Sizes

“…In particular, the leucine content ( 21 , 22 ), and the associated leucinemia ( 23 ), of the isolated protein source has been shown to potentiate postprandial MPS. Leucine is an anabolic signaling molecule acting through both mTORC1-dependent ( 24 ) and mTORC1-independent mechanisms ( 25 ) as well as a substrate to support the stimulation of MPS ( 26 ). While leucine serves both as a building block and signal, it is important to remember that all essential amino acids need to be available in order to maximize the anabolic potential of leucine on MPS ( 27 , 28 ).…”

Protein Source and Muscle Health in Older Adults: A Literature Review

“…Leucine not only activates MPS through mTOR complex 1 (mTORC1) [85], but also activates MPS through a mTORC1-independent processes [87,88]. But, it is important to note that leucine alone does not stimulate MPS; and actually require other amino acid to sustain anabolism [89]. For comparison, whey, casein, egg, soy, and pea protein isolate have 8.6 g, 5.8 g, 3.6 g, 5.0 g, 5.7 g of leucine per 100 g of food, respectively [79].…”