Oliver's mTOR Atlas Evidence Platform
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mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation

Zaufel A, Sun W, Pastore N, Taschler U, Wagner C, Hackl H, Sommer J, Silbert-Wagner D, Hengstler JG, Begher-Tibbe B, Stauber R, …, Moustafa T · 2026 · Science Advances · Atlas ID ZAU2026

What this study shows

Establishes a new mTORC1-TFEB/TFE3 signaling axis controlling hepatic bile acid metabolism. Depending on mTORC1 signaling state, mice show coordinated shifts in bile-acid species (non-12-OH vs 12-OH) via altered enzyme expression and cholesterol trafficking; these shifts are reversed by mTORC1 pathway deletion or rapamycin treatment. Dietary protein restriction (which inhibits mTORC1) produces a similar bile-acid shift in mice and correlates with improved metabolic outcomes in human MASLD patients, linking mTORC1 nutrient sensing directly to bile-acid homeostasis and fatty liver disease.

Abstract

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The mechanistic target of rapamycin complex 1 (mTORC1) integrates nutrient and hormonal cues to regulate hepatic lipid metabolism with major implications for metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that altered hepatic mTORC1-TFEB/TFE3 signaling is associated with coordinated remodeling of bile acid (BA) metabolism during metabolic adaptation. Our data support a model in which cross-talk between mTORC1 and TFEB/TFE3 is associated with divergent regulation of bile acid synthesis and transformation.

Read the full abstract on PubMed →

At a glance

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Evidence type A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse (liver-specific genetic mTORC1/TFEB manipulation, rapamycin treatment, dietary protein restriction); correlative human MASLD patient cohort); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type4 - Animal Study
Model systemMouse (liver-specific genetic mTORC1/TFEB manipulation, rapamycin treatment, dietary protein restriction); correlative human MASLD patient cohort
JournalScience Advances
Year2026
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1126/sciadv.aee1905 · PMID 42789715

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

People in the Atlas

  • Alex Zaufel first author · 1 study in the Atlas

    Researcher studying bile acid metabolism and mTORC1 signaling in liver disease

  • Tarek Moustafa last author · 1 study in the Atlas

    Researcher in hepatic metabolism and bile acid signaling

  • Andrea Ballabio 11 studies in the Atlas

    Discovered that the transcription factor TFEB is a master switch for building lysosomes (SAR2009) and for autophagy. His lab was one of the groups that showed in 2012 that mTORC1 keeps TFEB out of the nucleus from the lysosome surface, and later (2020) that constitutive TFEB activation drives the kidney disease of Birt-Hogg-Dubé syndrome

More: 25 other authors

No profile yet: Sun W, Pastore N, Taschler U, Wagner C, Hackl H, Sommer J, Silbert-Wagner D, Hengstler JG, Begher-Tibbe B, Stauber R, Kolb D, Troetzmueller M, Gottschalk B, Thorsheim C, Stange EL, Hornef MW, Pivovarova-Ramich O, Pfeiffer AFH, Matchett KP, Loft A, Herzig S, Henderson NC, Arany Z, Wolfrum C, Fickert P

Related studies

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Topics

TFEBRapamycinmTORC1

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.

InterventionLiver-specific genetic mTORC1/TFEB-TFE3 manipulation; rapamycin; dietary protein restriction
TargetmTORC1-TFEB/TFE3 axis; bile acid synthesis
ModelMouse liver; correlative human MASLD cohort
EffectmTORC1-TFEB/TFE3 signalling state is associated with shifts between 12-OH and non-12-OH bile acid species, attenuated by deletion or rapamycin.

Cite this paper

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Zaufel, A., Sun, W., Pastore, N., Taschler, U., Wagner, C., Hackl, H., Sommer, J., Silbert-Wagner, D., Hengstler, J. G., Begher-Tibbe, B., Stauber, R., Kolb, D., Troetzmueller, M., Gottschalk, B., Thorsheim, C., Stange, E. L., Hornef, M. W., Pivovarova-Ramich, O., Pfeiffer, A. F. H., Matchett, K. P., Loft, A., Herzig, S., Henderson, N. C., Ballabio, A., Arany, Z., Wolfrum, C., Fickert, P., & Moustafa, T. (2026). mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation. Science Advances. https://doi.org/10.1126/sciadv.aee1905

@article{ZAU2026,
  author       = {Zaufel, A. and Sun, W. and Pastore, N. and Taschler, U. and Wagner, C. and Hackl, H. and Sommer, J. and Silbert-Wagner, D. and Hengstler, J. G. and Begher-Tibbe, B. and Stauber, R. and Kolb, D. and Troetzmueller, M. and Gottschalk, B. and Thorsheim, C. and Stange, E. L. and Hornef, M. W. and Pivovarova-Ramich, O. and Pfeiffer, A. F. H. and Matchett, K. P. and Loft, A. and Herzig, S. and Henderson, N. C. and Ballabio, A. and Arany, Z. and Wolfrum, C. and Fickert, P. and Moustafa, T.},
  title        = {{mTORC1-TFEB/TFE3 signaling is associated with bile acid diversification during hepatic metabolic adaptation}},
  journal      = {Science Advances},
  year         = {2026},
  doi          = {10.1126/sciadv.aee1905},
  note         = {PMID: 42789715},
}

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 ZAU2026) [Data set]. https://mtor-atlas.org/study/ZAU2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ZAU2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ZAU2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ZAU2026/},
  doi          = {10.5281/zenodo.22059963}
}
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