Effects of oral phosphatidic acid feeding with or without whey protein on muscle protein synthesis and anabolic signaling in rodent skeletal muscle
Open accessAbstract
BACKGROUND: Phosphatidic acid (PA) is a diacyl-glycerophospholipid that acts as a signaling molecule in numerous cellular processes. Recently, PA has been proposed to stimulate skeletal muscle protein accretion, but mechanistic studies are lacking. Furthermore, it is unknown whether co-ingesting PA with other leucine-containing ingredients can enhance intramuscular anabolic signaling mechanisms. Thus, the purpose of this study was to examine if oral PA feeding acutely increases anabolic signaling markers and muscle protein synthesis (MPS) in gastrocnemius with and without whey protein concentrate (WPC). METHODS: Overnight fasted male Wistar rats (~250 g) were randomly assigned to four groups: control (CON, n = 6-13), PA (29 mg; n = 8), WPC (197 mg; n = 8), or PA + WPC (n = 8). Three hours post-feeding, gastrocnemius muscle was removed for markers of Akt-mTOR signaling, gene expression patterns related to skeletal muscle mass regulation and metabolism, and MPS analysis via the SUnSET method. RESULTS: Compared to CON rats, PA, WPC and PA + WPC resulted in a significant elevation in the phosphorylation of mTOR (Ser2481) and rps6 (Ser235/236) (p < 0.05) in the gastrocnemius though there were no differences between the supplemented groups. MPS levels in the gastrocnemius were significantly (p < 0.05) elevated in WPC versus CON rats, and tended to be elevated in PA versus CON rats (p = 0.08), though MPS was less in PA + WPC versus WPC rats (p < 0.05) in spite of robust increases in mTOR pathway activity markers in the former group. C2C12 myoblast data agreed with the in vivo data herein showing that PA increased MPS levels 51% (p < 0.001) phosphorylated p70s6k (Thr389) levels 67% (p < 0.001). CONCLUSIONS: Our results are the first in vivo evidence to demonstrate that PA tends to increases MPS 3 h post-feeding, though PA may delay WPC-mediated MPS kinetics within a 3 h post-feeding window.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PA has been reported to have a negative effect on WPC-stimulated protein synthesis.
“or even have a negative effect on WPC-stimulated protein synthesis”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [185]
PA lead to an ~50% reduction in the WPC-mediated MPS response.
“PA actually lead to an ~50% reduction in the WPC-mediated MPS response.”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [185]
WPC ingestion was the only intervention that significantly increased MPS 3h post administration.
“WPC ingestion was the only intervention that significantly increased MPS 3h post administration”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [185]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Dose translation from animal to human studies revisited.
Reagan‐Shaw, S., Nihal, M., & Ahmad, N. (2008) · The FASEB Journal · doi:10.1096/fj.07-9574lsf · Cited by 6,524 · see citing works
Watterson, K. R., Bestow, D., Gallagher, J. R., Hamilton, D. L., Ashford, F. B., Meakin, P. J., & Ashford, M. L. J. (2012) · Neurosignals · doi:10.1159/000334144 · Cited by 3,395 · see citing works
Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling
Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A., & Chen, J. (2001) · Science · doi:10.1126/science.1066015 · Cited by 1,055 · see citing works
mTORC1 controls the adaptive transition of quiescent stem cells from G0 to GAlert
Rodgers, J. T., King, K. Y., Brett, J. O., Cromie, M. J., Charville, G. W., Maguire, K. K., Brunson, C., Mastey, N., Liu, L., Tsai, C.-R., et al. (2014) · Nature · doi:10.1038/nature13255 · Cited by 776 · see citing works
Signaling functions of phosphatidic acid
WANG, X., DEVAIAH, S., ZHANG, W., & WELTI, R. (2006) · Progress in Lipid Research · doi:10.1016/j.plipres.2006.01.005 · Cited by 757 · see citing works
Signal integration by mTORC1 coordinates nutrient input with biosynthetic output
Dibble, C. C., & Manning, B. D. (2013) · Nature Cell Biology · doi:10.1038/ncb2763 · Cited by 716 · see citing works
Areta, J. L., Burke, L. M., Ross, M. L., Camera, D. M., West, D. W. D., Broad, E. M., Jeacocke, N. A., Moore, D. R., Stellingwerff, T., Phillips, S. M., et al. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2012.244897 · Cited by 495 · see citing works
Goodman, C. A., Mabrey, D. M., Frey, J. W., Miu, M. H., Schmidt, E. K., Pierre, P., & Hornberger, T. A. (2010) · The FASEB Journal · doi:10.1096/fj.10-168799 · Cited by 478 · see citing works
Self-citationHornberger, T. A., Chu, W. K., Mak, Y. W., Hsiung, J. W., Huang, S. A., & Chien, S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0600678103 · Cited by 312 · see citing works
Self-citationO’Neil, T. K., Duffy, L. R., Frey, J. W., & Hornberger, T. A. (2009) · The Journal of Physiology · doi:10.1113/jphysiol.2009.173609 · Cited by 227 · see citing works
Self-citationSoliman, G. A., Acosta-Jaquez, H. A., Dunlop, E. A., Üstünel, B. E., Maj, N. E., Tee, A. R., & Fingar, D. C. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.096222 · Cited by 227 · see citing works
Hulmi, J. J., Kovanen, V., Selänne, H., Kraemer, W. J., Häkkinen, K., & Mero, A. A. (2009) · Amino Acids · doi:10.1007/s00726-008-0150-6 · Cited by 189 · see citing works
mTOR function in skeletal muscle hypertrophy: Increased ribosomal RNA via cell cycle regulators
Nader, G. A., McLoughlin, T. J., & Esser, K. A. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00165.2005 · Cited by 166 · see citing works
You, J.-S., Lincoln, H. C., Kim, C.-R., Frey, J. W., Goodman, C. A., Zhong, X.-P., & Hornberger, T. A. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.531392 · Cited by 163 · see citing works
Self-citationYoon, M., Sun, Y., Arauz, E. J., Jiang, Y., & Chen, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.262816 · Cited by 134 · see citing works
Contractile and Nutritional Regulation of Human Muscle Growth
Rasmussen, B. B., & Phillips, S. M. (2003) · Exercise and Sport Sciences Reviews · doi:10.1097/00003677-200307000-00005 · Cited by 128 · see citing works
Herningtyas, E. H., Okimura, Y., Handayaningsih, A. E., Yamamoto, D., Maki, T., Iida, K., Takahashi, Y., Kaji, H., & Chihara, K. (2008) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.06.004 · Cited by 113 · see citing works
Lehman, N., Ledford, B., Difulvio, M., Frondorf, K., Mcphail, L., & Gomez-Cambronero, J. (2007) · The FASEB Journal · doi:10.1096/fj.06-6652com · Cited by 112 · see citing works
p21 is essential for normal myogenic progenitor cell function in regenerating skeletal muscle
Hawke, T. J., Meeson, A. P., Jiang, N., Graham, S. M., Hutcheson, K. A., DiMaio, J. M., & Garry, D. J. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00055.2003 · Cited by 110 · see citing works
Interleukin-6 mediates exercise preconditioning against myocardial ischemia reperfusion injury
McGinnis, G. R., Ballmann, C. G., Peters, B. A., Nanayakkara, G., Roberts, M. D., Amin, R., & Quindry, J. C. (2015) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00850.2014 · Cited by 84 · see citing works
Self-citationHawke, T. J., Jiang, N., & Garry, D. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209200200 · Cited by 82 · see citing works
Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway
Winter, J. N., Fox, T. E., KESTER, M. A., Jefferson, L. S., & Kimball, S. R. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00039.2010 · Cited by 82 · see citing works
Léger, B., Senese, R., Al-Khodairy, A., Dériaz, O., Gobelet, C., Giacobino, J., & Russell, A. P. (2009) · Muscle & Nerve · doi:10.1002/mus.21293 · Cited by 80 · see citing works
Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy
Joy, J. M., Gundermann, D. M., Lowery, R. P., Jäger, R., McCleary, S. A., Purpura, M., Roberts, M. D., Wilson, S. M., Hornberger, T. A., & Wilson, J. M. (2014) · Nutrition & Metabolism · doi:10.1186/1743-7075-11-29 · Cited by 76 · see citing works
Self-citationValverde, Á. M., Navarro, P., Teruel, T., Conejo, R., Benito, M., & Lorenzo, M. (1999) · Biochemical Journal · doi:10.1042/bj3370397 · Cited by 67 · see citing works
mTOR signaling: RAG GTPases transmit the amino acid signal
Shaw, R. J. (2008) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2008.09.005 · Cited by 58 · see citing works
Stuart, C. A., Howell, M. E. A., BAKER, J. D., Dykes, R., Duffourc, M. M., Ramsey, M. W., & Stone, M. H. (2009) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3181ad7f36 · Cited by 55 · see citing works
Nishioka, T., Frohman, M. A., Matsuda, M., & Kiyokawa, E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.153007 · Cited by 46 · see citing works
Hoffman, J. R., Stout, J. R., Williams, D. R., Wells, A. J., Fragala, M. S., Mangine, G. T., Gonzalez, A. M., Emerson, N. S., McCormack, W. P., Scanlon, T. C., et al. (2012) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-9-47 · Cited by 43 · see citing works
Self-citationMiyabara, E. H., Conte, T. C., da Silva, M. T., Baptista, I. L., Júnior, C. R. B., Fiamoncini, J., Lambertucci, R. H., Serra, C. S., Brum, P. C., Pithon‐Curi, T. C., et al. (2010) · Muscle & Nerve · doi:10.1002/mus.21754 · Cited by 40 · see citing works
Fan, Y.-P., & Weiss, R. H. (2004) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000114557.75244.5f · Cited by 40 · see citing works
Victoni, T., Gléonnec, F., Lanzetti, M., Tenor, H., Valença, S. S., Pôrto, L. C., Lagente, V., & Boichot, E. (2014) · PLoS ONE · doi:10.1371/journal.pone.0085243 · Cited by 37 · see citing works
Dalbo, V. J., Roberts, M. D., Hassell, S., & Kerksick, C. M. (2013) · European Journal of Nutrition · doi:10.1007/s00394-012-0349-x · Cited by 35 · see citing works
Self-citationEffects of Preexercise Feeding on Markers of Satellite Cell Activation
Roberts, M. D., Dalbo, V. J., Hassell, S. E., BROWN, R., & Kerksick, C. M. (2010) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3181da8a29 · Cited by 32 · see citing works
Self-citationMobley, C. B., Fox, C. D., Ferguson, B. S., Pascoe, C. A., Healy, J. C., McAdam, J. S., Lockwood, C. M., & Roberts, M. D. (2015) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-015-0076-9 · Cited by 24 · see citing works
Self-citationOlszewski, U., Deally, A., Tacke, M., & Hamilton, G. (2012) · Neoplasia · doi:10.1593/neo.12962 · Cited by 21 · see citing works
Postexercise Myogenic Gene Expression
Roberts, M. D., Dalbo, V. J., & Kerksick, C. M. (2011) · Exercise and Sport Sciences Reviews · doi:10.1097/jes.0b013e31822dad1f · Cited by 6 · see citing works
Self-citationMobley, C. B., Fox, C. D., Pascoe, C. A., Ferguson, B., Healy, J. C., Lockwood, C., & Roberts, M. (2014) · The FASEB Journal · doi:10.1096/fasebj.28.1_supplement.lb439 · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Advances in muscle health and nutrition: A toolkit for healthcare professionals
Prado, C. M., Landi, F., Chew, S. T. H., Atherton, P. J., Molinger, J., Ruck, T., & Gonzalez, M. C. (2022) · Clinical Nutrition · doi:10.1016/j.clnu.2022.07.041 · Cited by 237 · see citing works
New strategies in sport nutrition to increase exercise performance
Close, G. L., Hamilton, D. L., Philp, A., Burke, L. M., & Morton, J. P. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.01.016 · Cited by 221 · see citing works
Bond, P. (2016) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-016-0118-y · Cited by 121 · see citing works
Molecular Regulation of Exercise-Induced Muscle Fiber HypertrophyPreprint
Bamman, M. M., Roberts, B. M., & Adams, G. R. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a029751 · Cited by 95 · see citing works
Supplements with purported effects on muscle mass and strength
Valenzuela, P. L., Morales, J. S., Emanuele, E., Pareja-Galeano, H., & Lucia, A. (2019) · European Journal of Nutrition · doi:10.1007/s00394-018-1882-z · Cited by 78 · see citing works
“Nutraceuticals” in relation to human skeletal muscle and exercise
Deane, C. S., Wilkinson, D. J., Phillips, B. E., Smith, K., Etheridge, T., & Atherton, P. J. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00230.2016 · Cited by 73 · see citing works
A DGKζ-FoxO-ubiquitin proteolytic axis controls fiber size during skeletal muscle remodeling
You, J., Dooley, M. S., Kim, C.-R., Kim, E., Xu, W., Goodman, C. A., & Hornberger, T. A. (2018) · Science Signaling · doi:10.1126/scisignal.aao6847 · Cited by 50 · see citing works
Self-citationThe mechanistic and ergogenic effects of phosphatidic acid in skeletal muscle.
Shad, B. J., Smeuninx, B., Atherton, P., & Breen, L. (2015) · Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme · doi:10.1139/apnm-2015-0350 · Cited by 23 · see citing works
Paoli, A., Cerullo, G., Bianco, A., Neri, M., Gennaro, F., Charrier, D., & Moro, T. (2024) · Journal of Human Kinetics · doi:10.5114/jhk/186660 · Cited by 27 · see citing works
Wang, T., Wang, X., Zhou, H., Jiang, H., Mai, K., & He, G. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00221 · Cited by 22 · see citing works
Anabolic and Catabolic Signaling Pathways That Regulate Skeletal Muscle Mass
McCarthy, J. J., & Murach, K. A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-813922-6.00024-2 · Cited by 16 · see citing works
Gonzalez, A. M., Sell, K. M., Ghigiarelli, J. J., Kelly, C. F., Shone, E. W., Accetta, M. R., Baum, J. B., & Mangine, G. T. (2017) · Applied Physiology, Nutrition, and Metabolism · doi:10.1139/apnm-2016-0564 · Cited by 16 · see citing works
Smeuninx, B., Nishimura, Y., McKendry, J., Limb, M. C., Smith, K., Atherton, P. J., & Breen, L. (2018) · Clinical Nutrition · doi:10.1016/j.clnu.2018.06.963 · Cited by 12 · see citing works
Whey Protein Nutrition in Sports: Action Mechanisms and Gaps in Research
Pan, D., Zhang, Z., Liu, N., & Ashaolu, T. J. (2025) · Current Nutrition Reports · doi:10.1007/s13668-025-00673-w · Cited by 10 · see citing works
Skeletal muscle hypertrophy: molecular and applied aspects of exercise physiology
Arantes, V. H. F., da Silva, D. P., Alvarenga, R., Terra, A., Koch, A. J., Machado, M., & Pompeu, F. A. M. S. (2020) · German Journal of Exercise and Sport Research · doi:10.1007/s12662-020-00652-z · Cited by 10 · see citing works
Emerging Nutritional Supplements for Strength and Hypertrophy: An Update of the Current Literature
Gonzalez, A. M., Church, D. D., Townsend, J. R., & Bagheri, R. (2020) · Strength and conditioning journal · doi:10.1519/ssc.0000000000000552 · Cited by 8 · see citing works
Liao, K., Zhang, Q., Qiu, Y., Zhu, Y., Liu, Y., Huang, H., Chen, D., Ma, B., Zhang, L., Ran, Z., et al. (2023) · Aquaculture Research · doi:10.1155/2023/6666946 · Cited by 4 · see citing works
Jiang, H., Zhou, H., Liu, C., Wang, X., Mai, K., & He, G. (2021) · Journal of the World Aquaculture Society · doi:10.1111/jwas.12787 · Cited by 3 · see citing works
Takegaki, J., Yokokawa, T., Mori, R., Nakano, D., Matsushita, A., Koizumi, S., & Fujita, S. (2025) · Journal of Functional Foods · doi:10.1016/j.jff.2025.107063 · Cited by 2 · see citing works
Diacylglycerol kinases: Molecular mechanism of cellular and physiological functions
Kimura, T., & Epand, R. M. (2026) · Progress in Lipid Research · doi:10.1016/j.plipres.2025.101373 · Cited by 1 · see citing works
Nutritional Considerations for Concurrent Training
Etheridge, T., & Atherton, P. J. (2018) · Springer eBooks · doi:10.1007/978-3-319-75547-2_16
A Novel DGKK-FoxO-Ubiquitin Proteolytic Axis Controls Fiber Size During Skeletal Muscle RemodelingPreprint
You, J., Dooley, M. S., Kim, C.-R., Goodman, C. A., & Hornberger, T. A. (2018) · SSRN Electronic Journal · doi:10.2139/ssrn.3155631
Self-citationAspekte der Ernährung bei kombiniertem Ausdauer- und Krafttraining
Etheridge, T., & Atherton, P. J. (2023) · Springer eBooks · doi:10.1007/978-3-031-36310-8_16
- Authors
- Mobley, C. B., Hornberger, T. A., Fox, C. D., Healy, J. C., Ferguson, B. S., Lowery, R. P., McNally, R. M., Lockwood, C. M., Stout, J. R., Kavazis, A. N., Wilson, J. M., & Roberts, M. D.
- Affiliations
- Auburn University (US)
- University of Wisconsin–Madison (US)
- University of Tampa (US)
- 4LIFE Research, LLC Sandy UT USA
- University of Central Florida (US)
- Corresponding author
- Roberts, Michael D.
- ORCID
- Venue
- Journal of the International Society of Sports Nutrition
- Publisher
- Informa UK Limited
- Published
- 2015-10-20
- Volume
- 12
- Issue
- 1
- Pages
- 32-32
- ISSN
- 1550-2783 (ISSN-L)
- PMC
- PMC4537536
- OpenAlex
- W2128673831
- Cited by
- 23
- References
- 38
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 6 · 2017: 3 · 2016: 2 · 2015: 1
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the International Society of Sports Nutrition (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Journal of International Crisis and Risk Communication Research (submittedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-057347, R01AR057347)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
- Keywords
- phosphatidic acid, whey protein concentrate, muscle protein synthesis, skeletal muscle, mTOR signaling, Akt signaling, p70S6K, gastrocnemius, dietary supplementation, C2C12 myoblasts, sunset, leucine
- MeSH terms
- Whey Proteins, Mechanistic Target of Rapamycin Complex 1, Animals, Blood Glucose, Male, Muscle Proteins, Phosphatidic Acids, Phosphorylation, Protein Biosynthesis, Rats, Wistar, Muscle, Skeletal, Ribosomal Protein S6 Kinases, 70-kDa, Multiprotein Complexes, Proto-Oncogene Proteins c-akt, Glucose Transporter Type 4, Rats, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
