Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling

Atherton, Philip J.; Etheridge, Timothy; Watt, Peter; Wilkinson, Daniel J.; Selby, Anna; Rankin, Debbie; Smith, Kyle; Rennie, Michael J.

doi:10.3945/ajcn.2010.29819

Cited by 338 publications

(379 citation statements)

References 38 publications

(44 reference statements)

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“…Although MPS increases after oral consumption (Atherton et al 2010) or I.V infusions of essential AA are well accepted (Anthony et al 2000;Bennet et al 1990;Millward 2012) previous work by our group ) and others (Volpi et al 2000) has demonstrated 'anabolic resistance', whereby older men demonstrate blunted (compared to those in younger men) fed-state increases in MPS. Such anabolic resistance has not only been conjectured by us and others to contribute to the sarcopenia of ageing but it also appears to be a common feature of many kinds of muscle atrophy (e.g.…”

Section: Discussionmentioning

confidence: 98%

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Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

Phillips

Atherton

Varadhan

et al. 2016

Appl. Physiol. Nutr. Metab.

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Section: Discussionmentioning

confidence: 98%

“…This finding was based on a 2-hour window of fed-state MPS investigation, the postprandial period that has been well defined by our group (Atherton et al 2010;Mitchell et al 2015a;Mitchell et al 2015b). …”

Section: Discussionmentioning

confidence: 99%

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

Phillips

Atherton

Varadhan

et al. 2016

Appl. Physiol. Nutr. Metab.

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“…The anabolic effect of essential amino acids seems to level off at a total dose of 20-25 g protein day −1 (Tipton and Phillips, 2013). An oral bolus of whey protein has been shown to increase muscle protein synthesis by 300% while muscle protein breakdown is repressed by 50% in young men (Atherton et al, 2010). The increase in muscle proteins synthesis rate is mirrored by mTORC1 activation at least during the first 90 min of the response.…”

Section: Essential Amino Acidsmentioning

confidence: 95%

Molecular networks in skeletal muscle plasticity

Hoppeler

2016

Journal of Experimental Biology

163

117

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The skeletal muscle phenotype is subject to considerable malleability depending on use as well as internal and external cues. In humans, low-load endurance-type exercise leads to qualitative changes of muscle tissue characterized by an increase in structures supporting oxygen delivery and consumption, such as capillaries and mitochondria. High-load strength-type exercise leads to growth of muscle fibers dominated by an increase in contractile proteins. In endurance exercise, stress-induced signaling leads to transcriptional upregulation of genes, with Ca 2+ signaling and the energy status of the muscle cells sensed through AMPK being major input determinants. Several interrelated signaling pathways converge on the transcriptional co-activator PGC-1α, perceived to be the coordinator of much of the transcriptional and post-transcriptional processes. Strength training is dominated by a translational upregulation controlled by mTORC1. mTORC1 is mainly regulated by an insulin-and/or growth-factor-dependent signaling cascade as well as mechanical and nutritional cues. Muscle growth is further supported by DNA recruitment through activation and incorporation of satellite cells. In addition, there are several negative regulators of muscle mass. We currently have a good descriptive understanding of the molecular mechanisms controlling the muscle phenotype. The topology of signaling networks seems highly conserved among species, with the signaling outcome being dependent on the particular way individual species make use of the options offered by the multi-nodal networks. As a consequence, muscle structural and functional modifications can be achieved by an almost unlimited combination of inputs and downstream signaling events.

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“…mTORC1 signaling has consistently shown to be activated in response to both muscle loading (e.g., resistance exercise), and amino acid consumption/treatment (Marcotte, West, & Baar, 2015), and as such these stimuli represent excellent candidates as therapies for attenuating the muscle wasting associated with a number of disease states and ageing. Indeed, acute human studies have observed activation of mTORC1 and its downstream targets (e.g., p70S6K, rpS6, and 4EBP‐1) following ingestion of mixed amino acids, and this is coupled with an increase in muscle protein synthesis (MPS) in the ensuing 60–120 min (Atherton, Etheridge et al, 2010; Koopman et al, 2006; Paddon‐Jones et al, 2004; Volpi, Kobayashi, Sheffield‐Moore, Mittendorfer, & Wolfe, 2003). Furthermore, when human skeletal muscle undergoes loading prior to amino acid ingestion this effect on mTORC1 signaling and MPS is potentiated (Moore, Atherton, Rennie, Tarnopolsky, & Phillips, 2011; Witard et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro

Martin

Turner

Farrington

et al. 2017

Journal Cellular Physiology

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The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP‐1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co‐incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly‐controlled investigations into nutritional regulation of muscle physiology.

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Muscle full effect after oral protein: time-dependent concordance and discordance between human muscle protein synthesis and mTORC1 signaling

Abstract: 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.

Cited by 338 publications

References 38 publications

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men

Molecular networks in skeletal muscle plasticity

Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro

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