# Antrodia cinnamomea Extract Attenuates Obesity by Targeting Adipogenic Pathways and Gut Dysbiosis in High-Fat Diet-Fed Mice

**Authors:** Kuen-Tze Lin, Shih-Yu Lee, Lee Ya-Jy, Po-Jui Wu, Tsu-Chung Chang, Wen-Liang Chang, I-Chuan Yen

PMC · DOI: 10.3390/ijms26125856 · International Journal of Molecular Sciences · 2025-06-18

## TL;DR

Antrodia cinnamomea extract reduces obesity in mice by inhibiting fat cell development, improving lipid metabolism, and balancing gut bacteria.

## Contribution

This study reveals a new natural compound that targets multiple obesity-related mechanisms, including gut microbiota and adipogenesis.

## Key findings

- ACE inhibited adipocyte differentiation and lipid accumulation by downregulating PPARγ and C/EBPα in 3T3-L1 cells.
- ACE reduced body weight, adipose mass, and liver lipid accumulation in HFD-fed mice.
- ACE rebalanced gut microbiota by increasing beneficial bacteria and reducing pro-inflammatory species.

## Abstract

Obesity is a major metabolic disorder driven by excessive adipogenesis and lipid accumulation. This study investigated the anti-obesity effects and molecular mechanisms of Antrodia cinnamomea alcohol extract (ACE) in 3T3-L1 preadipocytes and a high-fat diet (HFD)-induced obesity mouse model. In vitro, Antrodia cinnamomea alcohol extract significantly inhibited adipocyte differentiation and lipid accumulation in 3T3-L1 cells by downregulating PPARγ and C/EBPα, while activating the AMPK pathway and suppressing MAPK signaling. In vivo, Antrodia cinnamomea alcohol extract administration reduced body weight, adipose tissue mass, and liver lipid accumulation in high-fat diet-fed mice, ameliorating non-alcoholic fatty liver disease (NAFLD) symptoms. Transcriptomic analysis of adipose tissue revealed that Antrodia cinnamomea alcohol extract modulated key gene expression profiles related to fatty acid metabolism and adipogenesis, suppressing lipid synthesis while enhancing β-oxidation. Furthermore, Antrodia cinnamomea alcohol extract rebalanced gut microbiota, increasing beneficial bacterial populations such as Akkermansia and Bifidobacterium, while reducing pro-inflammatory Escherichia-Shigella species. These findings demonstrate that Antrodia cinnamomea alcohol extract exerts multifaceted anti-obesity effects by regulating lipid metabolism, adipogenesis pathways, and gut microbiota composition, highlighting its potential as a natural therapeutic agent for obesity management.

## Linked entities

- **Genes:** PPARG (peroxisome proliferator activated receptor gamma) [NCBI Gene 5468], CEBPA (CCAAT enhancer binding protein alpha) [NCBI Gene 1050]
- **Diseases:** non-alcoholic fatty liver disease (MONDO:0013209), obesity (MONDO:0011122)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Ppara (peroxisome proliferator activated receptor alpha) [NCBI Gene 19013] {aka 4933429D07Rik, Nr1c1, PPAR-alpha, PPARalpha, Ppar}, Cebpa (CCAAT/enhancer binding protein alpha) [NCBI Gene 12606] {aka C/ebpalpha, CBF-A, Cebp}
- **Diseases:** NAFLD (MESH:D065626), inflammatory (MESH:D007249), metabolic disorder (MESH:D008659), Obesity (MESH:D009765)
- **Chemicals:** Fat (MESH:D005223), fatty acid (MESH:D005227), lipid (MESH:D008055), ACE (-)
- **Species:** Bifidobacterium (genus) [taxon 1678], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** 3T3-L1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0123)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12193264/full.md

## References

67 references — full list in the complete paper: https://tomesphere.com/paper/PMC12193264/full.md

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Source: https://tomesphere.com/paper/PMC12193264