Effects of exercise and amino acid intake on mechanisms regulating protein synthesis and breakdown in human muscle

Fredagen den 1 april klockan 09:00 disputerar Marcus Moberg i idrottsvetenskap. Avhandlingens titel är "Effects of exercise and amino acid intake on mechanisms regulating protein synthesis and breakdown in human muscle".

Marcus Moberg har skrivit en idrottsvetenskaplig avhandling inom fysiologi. Han tillhör GIH:s enhet för prestation och träning.

Disputationen äger rum fredag 1 april 2016 kl 09:00 i GIH:s aula.

Opponent är professor Jørgen Jensen, vid Norges idrottshögskola.

Huvudhandledare är professor Eva Blomstrand vid GIH och bihandledare professor Hans-Christer Holmberg, Mittuniversitetet.

Betygsämnden består av:

  • Karin Söderlund, docent, GIH
  • Jan Henriksson, professor emeritus, Karolinska Institutet
  • Folke Hammarqvist, docent, Karolinska Institutet

Läs mer om Marcus Moberg.

Läs avhandlingen i publikationsdatabasen DiVA.

Abstract

Läs pressmeddelandet om avhandingen 

Om avhandlingen 

Denna avhandling beskriver, och innehåller, fyra vetenskapliga artiklar, där syftet är att undersöka de molekylära mekanismerna som styr syntes och nedbrytning av protein i human skelettmuskel och hur dessa processer påverkas av olika typer av träning och aminosyror.

Omslag Marcus Mobergs avhandling

Det första arbetet undersöker om ett högintensivt konditionsträningspass utfört direkt innan ett styrketräningspass med benen påverkar anabola signalering i mTORC1 signalvägen, proteinsyntes samt genuttryck av markörer för proteinnedbrytning. Deltagarna i studien är unga, friska och vältränade individer som undersöks vid två separata tillfällen med utförandet av styrketräning med eller utan konditionstränings direkt innan.

Den andra delstudien har i princip samma upplägg och försökspersoner som det första arbetet, med den skillnaden att styrketräningen utförs med armarna och muskeln som undersöks är triceps brachii istället för vastus lateralis. Således undersöks den potentiella systemiska påverkan av konditionsträning på de styrketräningsinducerade akuta förändringarna i muskelcellen.

Det tredje arbetet involverar unga, friska och rekreationellt tränande individer. Här studeras vilken roll aminosyror leucine har bland de essentiella aminosyrornas förmåga att stimulera anabol signalering i samband styrketräning. I en randomiserad ordning genomför försökspersonerna två styrketräningspass där de i dryckesform får inta essentiella aminosyror med eller utan leucin närvarande.

Det sista arbetet jämför den akuta effekten av tillskott enbart leucin, grenade aminosyror, essentiella aminosyror samt placebo på anabola processer i samband med styrketräning. Studien involverar styrketräningsvana personer som studeras vid fyra separata tillfällen där de intar tillskotten i en randomiserad ordning.

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.

Adress till denna sida: www.gih.se/disputationMAMO