# Ellagic Acid Prevents Obesity in High-Fat Diet-Fed Rats by Ameliorating Oxidative Stress via Modulation of the PPARG/STAT3/p-AKT1 Axis

**Authors:** Yuancui Zheng, Qin Yuan, Shiyao Hu, Huiqun Wang

PMC · DOI: 10.3390/foods15050890 · Foods · 2026-03-05

## TL;DR

Ellagic acid helps prevent obesity in rats by reducing oxidative stress and inflammation through a specific biological pathway.

## Contribution

The study reveals a novel mechanism by which ellagic acid combats obesity via the PPARG/STAT3/p-AKT1 axis.

## Key findings

- EA reduced body weight and improved lipid profiles in high-fat diet-fed rats.
- EA attenuated intestinal oxidative stress and inflammation.
- EA modulated the PPARG/STAT3/p-AKT1 signaling pathway in intestinal tissues and cells.

## Abstract

This study investigated the protective effects and underlying mechanisms of ellagic acid (EA) against high-fat diet (HFD)-induced obesity. Using network pharmacology, STAT3 and AKT1 were identified as pivotal regulatory targets. In vivo experiments demonstrated that EA intervention significantly reduced body weight inducement, improved lipid profiles, and attenuated intestinal oxidative stress and inflammation in HFD-fed rats. Furthermore, EA restored intestinal architecture and mitochondrial morphology. Mechanistically, EA markedly downregulated the expression of PPARG, STAT3 and p-AKT1 in both intestinal tissues and TNF-α-stimulated HaCaT cells. Collectively, these findings suggest that EA prevents HFD-induced obesity by alleviating intestinal oxidative stress and mitochondrial dysfunction through the modulation of the PPARG/STAT3/p-AKT1 signaling axis. This study provides novel evidence for EA as a potential natural bioactive compound for the management of metabolic disorders.

## Linked entities

- **Genes:** PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468], STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774], AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207]
- **Chemicals:** ellagic acid (PubChem CID 5281855)
- **Diseases:** obesity (MONDO:0011122)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 25125], Pparg (peroxisome proliferator-activated receptor gamma) [NCBI Gene 25664] {aka PPARgamma2}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}
- **Diseases:** inflammation (MESH:D007249), mitochondrial dysfunction (MESH:D028361), Obesity (MESH:D009765), metabolic disorders (MESH:D008659)
- **Chemicals:** Fat (MESH:D005223), lipid (MESH:D008055), EA (MESH:D004610)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12984750/full.md

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12984750/full.md

## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC12984750/full.md

---
Source: https://tomesphere.com/paper/PMC12984750