MTORC1 SIGNALING-ACTIVATED INCREASES IN MUSCLE PROTEIN SYNTHESIS INDUCED BY LEUCINE AND PHOSPHATIDIC ACID: A BRIEF REVIEW

The mammalian target of rapamycin (mTOR) is a signaling network that functions to regulate various cellular and developmental processes. The stimuli of mechanical overload, nutrient sensing availability, and growth factors can up-regulate biomarkers within this signaling cascade to lead towards increases in protein translation initiation activity. mTOR is known to exist in two distinct multi-protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), which are known to differ in their subunit composition, respective sensitivity to rapamycin, upstream integrative patterns, regulation of substrates, and the control of biological processes. mTORC1 is known to be translocated to the lysosome where it is subsequently activated by Rheb,leucine-Ragulator/Rag GTPase parallel sensing pathways, and the hVps34-PLD axis. Phosphatidic acid (PA) is known as a diacyl-glycerophospholipid that is suggested to act as an intracellular lipid second messenger functioned to mediate signaling protein activity. PA is synthesized by various classes of enzymes such as phospholipase D (PLD) and directly activates mTORC1 by binding to the FKBP12-rapamycin-binding (FRB) domain of mTORC1. Interestingly, another alternative mechanism through which PA allegedly promotes activation of mTORC1 may also be through the MEK-ERK signaling pathway. Currently, there is a paucity of research on PA supplementation assisting in the mediation of protein synthesis via the PLD-PA axis. This brief review will highlight the mechanisms of action involved with mTORC1 activation via PA and the parallel nutrient sensing Rag/Ragulator complex. Lastly, this literature review will encompass the present research findings investigating the efficacy of L-leucine and PA supplementation on muscular strength, lean body mass and protein synthesis within human subjects.