Download Effects of exercise and amino acid intake on mechanisms

Effects of exercise and amino acid
intake on mechanisms regulating
protein synthesis and breakdown in
human muscle
av
Marcus Moberg
Akademisk avhandling
Avhandling för doktorsexamen i idrottsvetenskap
vid Gymnastik- och idrottshögskolan,
som enligt beslut av rektor kommer försvaras offentligt
fredagen den 1 april 2016 klockan 9:00,
i Aulan, vid Gymnastik- och idrottshögskolan, GIH, Stockholm.
Opponent: Professor Jørgen Jensen
Norges idrettshøgskole
Moberg, Marcus: Effects of exercise and amino acid intake on mechanisms regulating protein
synthesis and breakdown in human muscle.
Avhandlingsserie för Gymnastik- och idrottshögskolan Nr 07 (2016)
Abstract:
Skeletal muscle adapts differently to specific modes of exercise, where resistance training results
in muscle growth and endurance training induces mitochondrial biogenesis. These are results of
molecular events that occur after each exercise session, increasing the expression of specific genes
and the rate of both synthesis and breakdown of protein. The rate of protein synthesis is controlled
by the mTORC1 signaling pathway, which is potently stimulated by resistance exercise and amino
acid, and their combined effect is needed for muscle growth. The essential amino acids (EAA) are
responsible for the stimulation of protein synthesis and here leucine has been attributed specific
attention, but its particular role among the EAA, and the involvement of the other branched-chain
amino acids (BCAA) is unclear. Endurance exercise activates the protein AMPK which, in animal
models, has been shown to inhibit mTORC1 signaling and protein synthesis. Suggesting that
concurrent endurance and resistance exercise could restrain muscle growth, but it is unknown if this
mechanism is relevant in exercising human muscle. Little is known about the regulation of protein
breakdown and although much attention has been given the proteins MuRF-1 and MAFbx which
target proteins for degradation, their role requires further investigation. The aim of thesis was to
address the mentioned uncertainties by examining how different modes of exercise and amino acids
affect mTORC1 signaling, protein synthesis and markers of protein breakdown in human muscle.
In study I, the influence of high intensity endurance exercise on subsequent resistance exercised
induced mTORC1 signaling was examined. Despite robust activation of AMPK by the endurance
exercise there was no inhibition of mTORC1 signaling or protein synthesis during recovery from
resistance exercise. Study II utilized a similar set up, but with the difference that resistance exercise
was performed with the triceps. The cycling exercise reduced the resistance exercise stimulated
mTORC1 signaling immediately after the exercise, but during the recovery period mTORC1
signaling and protein synthesis was similar between trials. Concurrent exercise induced the mRNA
expression of MuRF-1 and that of PGC-1α, the master regulator of mitochondrial biogenesis, in
both studies, despite that the exercise modes in study II were separated between legs and arms. In
study III, the effect of an EAA supplement with or without leucine, in the stimulation of mTORC1
signaling in connection with resistance exercise was examined. Intake of EAA robustly stimulated
mTORC1 signaling after exercise, but this was only minor when leucine was excluded from
the supplement. In study IV, subjects were supplied with leucine, BCAA, EAA or placebo in a
randomized fashion during four sessions of resistance exercise. Leucine alone stimulated mTORC1
signaling after the exercise, but both the amplitude and extent of stimulation was substantially
greater with EAA, an effect that was largely mediated by the BCAA as a group.
In conclusion, endurance exercise prior to resistance exercise using the leg or arm muscles does not
affect mTORC1 signaling or protein synthesis during the three hour recovery period from exercise,
supporting compatibility between resistance- and endurance exercise induced signaling. Concurrent
exercise increases the expression of the proteolytic marker MuRF-1 compared to resistance exercise
only, which could indicate both and increased demand of cellular adaptive remodeling or a more
direct detrimental proteolytic effect. Leucine is crucial among the EAA in the stimulation of
mTORC1 signaling after exercise, its effect is however potentiated by intake of the remaining
EAA. As a supplement a mixture of EAA must be regarded preferable, although the effect is largely
mediated by the BCAA as a group.
Keywords: Resistance exercise, concurrent exericse, leucine, BCAA, mTORC1 signaling, protein
synthesis, MuRF-1, PGC-1alpha
ISBN: 978-91-980862-6-3
http://urn.kb.se/resolve?urn=urn:nbn:se:gih:diva-4371
Marcus Moberg, Gymnastik- och idrottshögskolan, Lidingövägen 1, Box 5626,
SE-114 86 Stockholm, Sweden, e-mail: [email protected]