Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1.

Kalafut KC, Cormerais Y, Cissé MY, Lapp SC, Inouye KE, Hotamışlıgil GS, Manning BD · 2026 · Nature Communications · Atlas ID KAL2026

What this study shows

In liver-specific mouse genetic models, AKT-mediated TSC2 phosphorylation is the main route by which insulin induces hepatic mTORC1, but is dispensable for feeding-induced activation; postprandial mTORC1 activation instead requires dietary protein, and hepatic mTORC1 signalling is not elevated in diet-induced obesity despite impaired insulin/glucose homeostasis.

Abstract

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The nutrient-sensing mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway controls cellular and organismal growth and metabolism, and aberrant activation is linked to human disease, including metabolic disease. Cellular studies have established regulatory mechanisms influencing mTORC1 activation, but the physiological signals that control mTORC1 at the organismal and tissue levels are less well-defined. mTORC1 is dynamically regulated by fasting and feeding in metabolic tissues, with both nutrients and insulin proposed to activate mTORC1 in response to feeding.

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: Mouse, liver-specific AKT/TSC2 genetic models); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse, liver-specific AKT/TSC2 genetic models
Journal	Nature Communications
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/s41467-026-77216-6 · PMID 42811030

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Liver-specific AKT and TSC2 genetic manipulation; dietary protein and feeding/fasting manipulation
Target	Hepatic mTORC1 via the AKT-TSC2 axis
Model	Mouse (liver-specific)
Effect	AKT-TSC2 phosphorylation is the main insulin route to hepatic mTORC1 but is dispensable for feeding-induced activation, which instead requires dietary protein; hepatic mTORC1 was not elevated in diet-induced obesity.

In the Atlas

Links in the pathway map

Supports Akt/PKB inhibits TSC1/TSC2

Cite this paper

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Kalafut, K. C., Cormerais, Y., Cissé, M. Y., Lapp, S. C., Inouye, K. E., Hotamışlıgil, G. S., & Manning, B. D. (2026). Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1. Nature Communications. https://doi.org/10.1038/s41467-026-77216-6

@article{KAL2026,
  author       = {Kalafut, K. C. and Cormerais, Y. and Cissé, M. Y. and Lapp, S. C. and Inouye, K. E. and Hotamışlıgil, G. S. and Manning, B. D.},
  title        = {{Dietary protein governs the role of insulin signaling in the postprandial regulation of hepatic mTORC1}},
  journal      = {Nature Communications},
  year         = {2026},
  doi          = {10.1038/s41467-026-77216-6},
  note         = {PMID: 42811030},
}

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 KAL2026) [Data set]. https://mtor-atlas.org/study/KAL2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_KAL2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record KAL2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/KAL2026/},
  doi          = {10.5281/zenodo.22059963}
}

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