To understand why one may even expect that there was a synergism between whey protein (or leucine) and phosphatidic acid, one has to be aware of the fact that both trigger mTOR, albeit via different pathways: While leucine activates mTOR through RAG GTPase, PA is thought to independently activate mTOR through competitive binding with the mTOR inhibitor FKBP38. As Mobley et al. point out in the introduction to their latest paper in the Journal of the ISSN it does thus "stand[...] to reason that whey protein could synergistically activate mTOR if co-ingested with PA" (Mobley. 2015). Accordingly, ...
"the purpose of this study was to examine if PA acutely increases anabolic signaling markers and muscle protein synthesis (MPS) in gastrocnemius with and without whey protein concentrate (WPC) supplementation" (Mobley. 2015).In view of the fact that previous studies did not do a detailed analysis of the skeletal muscle transcriptomic response to PA and considering the fact that the latter may be important with respect to finding explanations for any - positive or negative - findings, Mobley et al. ran detailed analysis of the skeletal muscle mRNA response to PA and/or WPC, as well. Their goal was to assess whether PA or PA + whey would affect key genes involved in muscle mass maintenance (myostatin (Mstn) and p21Cip1), metabolism (PGC-1α and GLUT-4), and skeletal muscle atrophy (Atrogin-1 and MuRF-1). To get this data, the researchers randomly assigned male Wistar rats to four different treatments groups groups in which they were gavaged with one of the following "supplements":
- control (CON) - 1 ml of tap water
- phosphatidic acid (PA) - 0.029 g soy-derived PA (S-PA, Mediator®, ChemiNutra, Austin, TX, USA) suspended in 1 ml of tap water; this being a human equivalent dose of 1.5 g per the species conversion calculations of ReaganShaw et al. (learn more)
- whey protein concentrate (WPC) - 0.193 g WPC (standardized to 80 %, donated graciously by C.M.L.) suspended in 1 ml of tap water; this being a human equivalent dose of 10 g
- combined (PA + WPC) - 0.029 g soy-derived PA + 0.193 g WPC suspended in 1 ml of tap water