The Role of Diacylglycerol Kinase ζ and Phosphatidic Acid in the Mechanical Activation of Mammalian Target of Rapamycin (mTOR) Signaling and Skeletal Muscle Hypertrophy

You, Jae‐Sung; Lincoln, Hannah C.; Kim, Chan-Ran; Frey, John W.; Goodman, Craig A.; Zhong, Xiao‐Ping; Hornberger, Troy A.

doi:10.1074/jbc.m113.531392

Cited by 138 publications

(135 citation statements)

References 57 publications

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“…When amino acids are above a certain threshold these Rags dimerise with the correct GTP loading status in such a way as to allow mTORC1 complex assembly [101]. As we mentioned the amino acid induced activation of mTORC1 is distinct from the mechanical activation of mTORC1, which again is not yet fully defined, but is thought to be dependent upon the secondary messenger phosphatidic acid (PA) derived from diacylglycerol kinase (DGK) [102]. Because the mechanically sensitive pathways and the resistance exercise pathways are distinct, consuming essential amino acids following resistance exercise significantly activates mTORC1 above resistance exercise alone [103].…”

Section: The Molecular Regulation Of Resistance Training Adaptation mentioning

confidence: 99%

New strategies in sport nutrition to increase exercise performance

Hamilton

Philp

et al. 2016

Free Radical Biology and Medicine

178

118

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Despite over 50 years of research, the field of sports nutrition continues to grow at a rapid rate. Whilst the traditional research focus was one that centred on strategies to maximize competition performance, emerging data in the last decade has demonstrated how both macronutrient and micronutrient availability can play a prominent role in regulating those cell signalling pathways that modulate skeletal muscle adaptations to endurance and resistance training. Nonetheless, in the context of exercise performance, it is clear that carbohydrate (but not fat) still remains king and that carefully chosen ergogenic aids (e.g. caffeine, creatine, sodium bicarbonate, beta-alanine, nitrates) can all promote performance in the correct exercise setting. In relation to exercise training, however, it is now thought that strategic periods of reduced carbohydrate and elevated dietary protein intake may enhance training adaptations whereas high carbohydrate availability and antioxidant supplementation may actually attenuate training adaptation. Emerging evidence also suggests that vitamin D may play a regulatory role in muscle regeneration and subsequent hypertrophy following damaging forms of exercise. Finally, novel compounds (albeit largely examined in rodent models) such as epicatechins, nicotinamide riboside, resveratrol, β-hydroxy β-methylbutyrate, phosphatidic acid and ursolic acid may also promote or attenuate skeletal muscle adaptations to endurance and strength training. When taken together, it is clear that sports nutrition is very much at the heart of the Olympic motto, Citius, Altius, Fortius (faster, higher, stronger).

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Section: The Molecular Regulation Of Resistance Training Adaptation mentioning

confidence: 99%

New strategies in sport nutrition to increase exercise performance

Hamilton

Philp

et al. 2016

Free Radical Biology and Medicine

178

118

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“…Activation of mTORC1 has been linked to a myriad of energetic and hormonal signals (e.g. growth factors, amino acids and mechanical stimuli) that converge on the lysosome to augment protein synthesis by enhancing its interaction with two direct activators, a small GTPase called Rheb (Inoki et al, 2003a,b) and the glycerophospholipid phosphatidic acid (PA) (Sun et al, 2008;Yoon et al, 2011;You et al, 2014).…”

Section: Cellular Regulation Of Exercise Training Adaptation: a Primermentioning

confidence: 99%

Effects of skeletal muscle energy availability on protein turnover responses to exercise

Smiles

Hawley

Camera

2016

Journal of Experimental Biology

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Skeletal muscle adaptation to exercise training is a consequence of repeated contraction-induced increases in gene expression that lead to the accumulation of functional proteins whose role is to blunt the homeostatic perturbations generated by escalations in energetic demand and substrate turnover. The development of a specific 'exercise phenotype' is the result of new, augmented steady-state mRNA and protein levels that stem from the training stimulus (i.e. endurance or resistance based). Maintaining appropriate skeletal muscle integrity to meet the demands of training (i.e. increases in myofibrillar and/or mitochondrial protein) is regulated by cyclic phases of synthesis and breakdown, the rate and turnover largely determined by the protein's half-life. Cross-talk among several intracellular systems regulating protein synthesis, breakdown and folding is required to ensure protein equilibrium is maintained. These pathways include both proteasomal and lysosomal degradation systems (ubiquitin-mediated and autophagy, respectively) and the protein translational and folding machinery. The activities of these cellular pathways are bioenergetically expensive and are modified by intracellular energy availability (i.e. macronutrient intake) and the 'training impulse' (i.e. summation of the volume, intensity and frequency). As such, exercisenutrient interactions can modulate signal transduction cascades that converge on these protein regulatory systems, especially in the early post-exercise recovery period. This review focuses on the regulation of muscle protein synthetic response-adaptation processes to divergent exercise stimuli and how intracellular energy availability interacts with contractile activity to impact on muscle remodelling.

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“…The wheel-running protocol has been described previously (23). An acute stretching protocol of skeletal muscle was performed as previously described (26). Muscle wet weights and cross-sections were measured as previously described (5).…”

Section: Methodsmentioning

confidence: 99%

G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy

White

Wrann

Rao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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103

100

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Peroxisome proliferator-activated receptor gamma coactivator 1-alpha 4 (PGC-1α4) is a protein isoform derived by alternative splicing of the PGC1α mRNA and has been shown to promote muscle hypertrophy. We show here that G protein-coupled receptor 56 (GPR56) is a transcriptional target of PGC-1α4 and is induced in humans by resistance exercise. Furthermore, the anabolic effects of PGC-1α4 in cultured murine muscle cells are dependent on GPR56 signaling, because knockdown of GPR56 attenuates PGC-1α4-induced muscle hypertrophy in vitro. Forced expression of GPR56 results in myotube hypertrophy through the expression of insulin-like growth factor 1, which is dependent on Gα12/13 signaling. A murine model of overload-induced muscle hypertrophy is associated with increased expression of both GPR56 and its ligand collagen type III, whereas genetic ablation of GPR56 expression attenuates overload-induced muscle hypertrophy and associated anabolic signaling. These data illustrate a signaling pathway through GPR56 which regulates muscle hypertrophy associated with resistance/loading-type exercise.GPR56 | mTOR | Gα12/13 | muscle hypertrophy | overload

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The Role of Diacylglycerol Kinase ζ and Phosphatidic Acid in the Mechanical Activation of Mammalian Target of Rapamycin (mTOR) Signaling and Skeletal Muscle Hypertrophy

Cited by 138 publications

References 57 publications

New strategies in sport nutrition to increase exercise performance

New strategies in sport nutrition to increase exercise performance

Effects of skeletal muscle energy availability on protein turnover responses to exercise

G protein-coupled receptor 56 regulates mechanical overload-induced muscle hypertrophy

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