RESEARCH Open Access Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy Jordan M Joy 1 , David M Gundermann 2 , Ryan P Lowery 1 , Ralf Jäger 3 , Sean A McCleary 1 , Martin Purpura 3 , Michael D Roberts 4 , Stephanie MC Wilson 5 , Troy A Hornberger 2 and Jacob M Wilson 1* Abstract Introduction: The lipid messenger phosphatidic acid (PA) plays a critical role in the stimulation of mTOR signaling. However, the mechanism by which PA stimulates mTOR is currently unknown. Therefore, the purpose of this study was to compare the effects of various PA precursors and phospholipids on their ability to stimulate mTOR signaling and its ability to augment resistance training-induced changes in body composition and performance. Methods: In phase one, C 2 C 12 myoblasts cells were stimulated with different phospholipids and phospholipid precursors derived from soy and egg sources. The ratio of phosphorylated p70 (P-p70-389) to total p70 was then used as readout for mTOR signaling. In phase two, resistance trained subjects (n = 28, 21 ± 3 years, 77 ± 4 kg, 176 ± 9 cm) consumed either 750 mg PA daily or placebo and each took part in an 8 week periodized resistance training program. Results: In phase one, soy-phosphatidylserine, soy-Lyso-PA, egg-PA, and soy-PA stimulated mTOR signaling, and the effects of soy-PA (+636%) were significantly greater than egg-PA (+221%). In phase two, PA significantly increased lean body mass (+2.4 kg), cross sectional area (+1.0 cm), and leg press strength (+51.9 kg) over placebo. Conclusion: PA significantly activates mTOR and significantly improved responses in skeletal muscle hypertrophy, lean body mass, and maximal strength to resistance exercise. Keywords: Supplementation, Skeletal muscle, Protein synthesis, Phospholipid, Ergogenic aid Introduction Increasing or maintaining skeletal muscle mass is an im- portant target for a variety of populations ranging from athletes to the elderly. Skeletal muscle mass is largely dependent upon muscle protein synthesis (MPS), and a protein kinase called the mechanistic target of rapamy- cin (mTOR) has been widely recognized as a key regula- tor of muscle growth. Specifically, elevations in energy status [1-3], amino acids [4,5], and growth factors [6,7] can increase MPS through an mTOR-dependent me- chanism. Furthermore, several studies have also shown that signaling by mTOR is required for mechanically- induced increases in MPS and the ultimate hypertrophic response [8-11]. Phosphatidic acid (PA) is a diacyl-glycerophospholipid, in which two fatty acids and a phosphate group are cova- lently bonded to a glycerol molecule through ester link- ages. PA can act as a signaling lipid, it is a precursor for the biosynthesis of other lipids, and it is a major constitu- ent of cell membranes. Recent studies have shown that mechanical stimuli can induce an increase in the intracel- lular levels of PA and that the increase in intracellular PA contributes to the activation of mTOR-dependent signa- ling events such as ribosomal S6 kinase 1 (p70) threonine 389 phosphorylation (P-p70-389) [12]. It has also been shown that PA can directly bind to the FKBP12 · rapamy- cin binding (FRB) domain of mTOR, and in doing so, it activates mTOR signaling [13,14]. It has also been shown that exogenous sources of PA can promote the activation of mTOR signaling, yet the effects of exogenous PA ap- pear to be driven through multiple mechanisms. For ex- ample, Winter and colleagues [15] have demonstrated that the exogenous addition of PA to fibroblasts results in the * Correspondence: jmwilson@ut.edu 1 Department of Health Sciences and Human Performance, The University of Tampa, 401 W. Kennedy Blvd., Box 30 F, Tampa, FL 33606, USA Full list of author information is available at the end of the article © 2014 Joy et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Joy et al. Nutrition & Metabolism 2014, 11:29 http://www.nutritionandmetabolism.com/content/11/1/29