Feeding-Induced Muscle mTORC1 Signaling Regulates Postprandial Protein Synthesis and Endurance but Not Muscle Size

Lapp SC, Kalafut KC, Cissé MY, Tighanimine K, Rosenthal DM, Doxsey W, Hui S, Inouye KE, Morrow CE, Cormerais Y, Manning BD · 2026 · JCI insight · Atlas ID LAP2026

What this study shows

Using a mouse model expressing an AKT-nonphosphorylatable TSC2 mutant specifically in skeletal muscle, the Manning lab genetically separated feeding-induced from contraction-induced mTORC1 activation. AKT-mediated TSC2 phosphorylation is required for feeding (but not contraction) to activate muscle mTORC1 and drive postprandial protein synthesis — yet mice lacking this feeding-induced signal have normal muscle mass and myofiber size, and instead show improved maximal endurance capacity with a modest rise in mitochondrial content. The finding dissociates mTORC1's role in postprandial anabolism from its role in maintaining steady-state muscle mass, and is a directly relevant data point for whether the pattern/source of mTORC1 activation (feeding vs. mechanical) — not just its average level — shapes downstream outcomes.

Abstract

ShowHide

Activation of the mechanistic target of rapamycin (mTOR) complex1 (mTORC1) promotes muscle protein synthesis, mass, and function. Muscle mTORC1 can be activated by feeding and contraction. Here, muscle mTORC1 signaling, protein synthesis, mass, and function are characterized in a genetic mouse model that separates these two major modes of muscle mTORC1 regulation.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: SkM-TSC2-5A knock-in mice (AKT-phosphorylation-resistant TSC2, skeletal muscle-specific) vs SkM-TSC2-WT littermates, both sexes); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	SkM-TSC2-5A knock-in mice (AKT-phosphorylation-resistant TSC2, skeletal muscle-specific) vs SkM-TSC2-WT littermates, both sexes
Journal	JCI insight
Year	2026
Peer reviewed	Yes
Record last updated	2026-08-22
Source	DOI 10.1172/jci.insight.210523 · PMID 42720990

Extracted findings

Intervention	Genetic knock-in of AKT-phosphorylation-resistant TSC2 (5A mutant), muscle-specific — separates feeding- from contraction-induced mTORC1 activation
Target	AKT-TSC2-mTORC1 axis in skeletal muscle
Model	Mouse (skeletal muscle-specific knock-in, both sexes)
Effect	Blocked feeding-induced (not contraction-induced) mTORC1 activation and postprandial protein synthesis; muscle mass/myofiber size unchanged; improved maximal endurance and modestly increased mitochondrial content

Cite this paper

ShowHide

Lapp, S. C., Kalafut, K. C., Cissé, M. Y., Tighanimine, K., Rosenthal, D. M., Doxsey, W., Hui, S., Inouye, K. E., Morrow, C. E., Cormerais, Y., & Manning, B. D. (2026). Feeding-Induced Muscle mTORC1 Signaling Regulates Postprandial Protein Synthesis and Endurance but Not Muscle Size. JCI insight. https://doi.org/10.1172/jci.insight.210523

@article{LAP2026,
  author       = {Lapp, S. C. and Kalafut, K. C. and Cissé, M. Y. and Tighanimine, K. and Rosenthal, D. M. and Doxsey, W. and Hui, S. and Inouye, K. E. and Morrow, C. E. and Cormerais, Y. and Manning, B. D.},
  title        = {{Feeding-Induced Muscle mTORC1 Signaling Regulates Postprandial Protein Synthesis and Endurance but Not Muscle Size}},
  journal      = {JCI insight},
  year         = {2026},
  doi          = {10.1172/jci.insight.210523},
  note         = {PMID: 42720990},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record LAP2026) [Data set]. https://mtor-atlas.org/study/LAP2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LAP2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record LAP2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LAP2026/},
  doi          = {10.5281/zenodo.22059963}
}