Oliver's mTOR Atlas Evidence Platform
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Urolithin A activates mitophagy via the AMPK-mTOR axis and modulates the gut-ceramide axis to ameliorate cardiac remodeling in HFpEF

Hangyul Song, Chahyeon Yun, Yunju Choi, Wooju Jeong, Yumin Kim, Jaeyoung Kim, Ju-Yeon Lee, Dongryeol Ryu, Sang-Wook Park, Chang-Myung Oh · 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 type4 - Animal Study
Model systemMouse (HFpEF two-hit model)
JournalExperimental and Molecular Medicine
Year2026
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1038/s12276-026-01776-2 · PMID 42432192

Extracted findings

InterventionUrolithin A (gut microbiome-derived compound)
TargetAMPK / mTOR / ULK1 / mitophagy / ceramide axis
ModelMouse
EffectImproved diastolic function, reduced cardiac hypertrophy and fibrosis via mitophagy restoration; reduced ceramide accumulation

In the Atlas

Related topics

MitophagyULK1mTORAutophagyAMPKUrolithin A

More studies on this topic

Cite this paper

ShowHide 
Hangyul Song, Chahyeon Yun, Yunju Choi, Wooju Jeong, Yumin Kim, Jaeyoung Kim, Ju-Yeon Lee, Dongryeol Ryu, Sang-Wook Park, & Chang-Myung Oh (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       = {Hangyul Song and Chahyeon Yun and Yunju Choi and Wooju Jeong and Yumin Kim and Jaeyoung Kim and Ju-Yeon Lee and Dongryeol Ryu and Sang-Wook Park and Chang-Myung Oh},
  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}
}