Berberine is a plant-derived isoquinoline alkaloid with anti-inflammatory and metabolic regulatory properties. Nevertheless, its role in immune–vascular remodeling in obese adipose tissue remains unclear. This study investigated whether berberine ameliorates obesity-induced adipose tissue remodeling by regulating macrophage activation and vascular dysfunction in a high-fat diet (HFD)-induced obesity model. Male C57BL/6 mice were assigned to normal diet, HFD, or HFD plus berberine treatment groups for eight weeks. Whole-mount immunofluorescence staining, vascular permeability assays, ELISA, and quantitative real-time PCR were performed using epididymal adipose tissue. HFD feeding markedly increased adipocyte hypertrophy, PECAM-1-positive vascular expansion, vascular leakage, and macrophage infiltration. Berberine significantly reduced adipocyte enlargement, pathological vascular remodeling, and Evans blue dye extravasation, indicating improved endothelial barrier integrity. Berberine also suppressed M1-associated (TNF-α, IL-1β, CD11c, and CCL2) and M2-associated (arginase-1, CD206, Fizz1, and TGF-β1) macrophage markers, suggesting the inhibition of global macrophage hyperactivation rather than phenotype-specific polarization. LYVE-1-positive cells were minimally affected by the berberine treatment. Hence, berberine alleviates obesity-associated adipose tissue inflammation through coordinated attenuation of macrophage-driven inflammatory responses and pathological vascular remodeling.

Abstract
I. Introduction
II. Materials and methods
    1. Animal experiments
    2. Histopathological analysis
    3. Whole mount fluorescent immunohistochemistry
    4. Quantitative real-time PCR
    5. Enzyme-linked immunosorbent assay (ELISA)
    6. Vascular permeability analysis
    7. Statistical analysis
III. Results and Discussion
    1. Berberine attenuates adipocyte hypertrophy andmacrophage infiltration in HFD-induced obese mice
    2. Berberine attenuates obesity-associated vascularremodeling in epididymal adipose tissue
    3. Berberine suppresses macrophage activation inobese adipose tissue
    4. Berberine suppresses macrophage-associatedinflammatory responses in obese adipose tissue
    5. Berberine decreases vascular permeability in obeseadipose tissue
IV. Summary and Conclusion
Acknowledgement
Conflict of Interest
References

• 김민정(노화연구단 한국식품연구원) | Min Jung Kim (Research Group of Aging, Korea Food Research Institute, Jeollabuk-do, Republic of Korea)
• 이애신(노화연구단 한국식품연구원) | Ae Sin Lee (Research Group of Aging, Korea Food Research Institute, Jeollabuk-do, Republic of Korea) Corresponding author