Urolithin A activates mitophagy via the AMPK-mTOR axis and modulates the gut-ceramide axis to ameliorate cardiac remodeling in HFpEF

Song H, Yun C, Choi Y, Jeong W, Kim Y, Kim J, Lee JY, Ryu D, Park SW, Oh CM · 2026 · Experimental and Molecular Medicine · Atlas ID SONH2026

What this study shows

Urolithin A ameliorates HFpEF cardiac remodeling in mice by activating AMPK and inhibiting mTOR to restore mitophagic flux, while simultaneously remodeling the gut microbiome-ceramide axis to reduce lipotoxic stress.

Abstract

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In a two-hit HFpEF mouse model (high-fat diet + L-NAME), urolithin A (UA) alleviated diastolic dysfunction, cardiac hypertrophy, and fibrosis. UA activated AMPK signaling while inhibiting mTOR, promoting ULK1-dependent autophagy initiation and restoring impaired mitophagic flux. Multi-omics revealed UA remodels the gut microbiome-ceramide axis, reducing circulating ceramide accumulation and lipotoxic stress. Single-nucleus transcriptomics in human iPSC-derived cardiomyocytes confirmed attenuation of fibrosis-related cellular programming.

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 (HFpEF two-hit model)); 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 (HFpEF two-hit model)
Journal	Experimental and Molecular Medicine
Year	2026
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/s12276-026-01776-2 · PMID 42432192

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	Urolithin A (gut microbiome-derived compound)
Target	AMPK / mTOR / ULK1 / mitophagy / ceramide axis
Model	Mouse
Effect	Improved diastolic function, reduced cardiac hypertrophy and fibrosis via mitophagy restoration; reduced ceramide accumulation

In the Atlas

Cite this paper

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Song, H., Yun, C., Choi, Y., Jeong, W., Kim, Y., Kim, J., Lee, J. Y., Ryu, D., Park, S. W., & Oh, C. M. (2026). Urolithin A activates mitophagy via the AMPK-mTOR axis and modulates the gut-ceramide axis to ameliorate cardiac remodeling in HFpEF. Experimental and Molecular Medicine. https://doi.org/10.1038/s12276-026-01776-2

@article{SONH2026,
  author       = {Song, H. and Yun, C. and Choi, Y. and Jeong, W. and Kim, Y. and Kim, J. and Lee, J. Y. and Ryu, D. and Park, S. W. and Oh, C. M.},
  title        = {{Urolithin A activates mitophagy via the AMPK-mTOR axis and modulates the gut-ceramide axis to ameliorate cardiac remodeling in HFpEF}},
  journal      = {Experimental and Molecular Medicine},
  year         = {2026},
  doi          = {10.1038/s12276-026-01776-2},
  note         = {PMID: 42432192},
}

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 SONH2026) [Data set]. https://mtor-atlas.org/study/SONH2026/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_SONH2026,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record SONH2026},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/SONH2026/},
  doi          = {10.5281/zenodo.22059963}
}

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