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From brown to white: Brown adipose tissue endothelial cells whiten in culture conditions.
Mol. Metab. 107:102349 (2026)
Endothelial cells (ECs) are central regulators of vascular and metabolic homeostasis, yet their organ- and depot-specific diversity remains underexplored. Two major types of adipose tissue (AT) can be distinguished that differ substantially in their physiological function and vascularization: white AT (WAT), which is the major energy storage and brown AT (BAT), which is highly vascularized and dissipates energy [1-5]. While ECs from these depots likely contribute to adipose function, their characterization has been hindered by technical limitations in isolation and culture. Here, we establish a protocol for isolating and expanding ECs from murine BAT and WAT, enabling transcriptomic and functional analyses across depots. We demonstrate that freshly isolated BAT-ECs express depot-enriched gene signatures, including Rgcc, Cdkn1c, Tcf15, Meox2, and Efnb1, several of which are dynamically regulated during cold-induced BAT activation. These findings reveal novel BAT-EC markers and highlight specialized endothelial programs that may support BAT function. However, we also uncover that culturing BAT-ECs profoundly remodels EC identity. Transcriptomic profiling shows that BAT-ECs rapidly downregulate BAT-enriched endothelial markers and acquire features resembling WAT-ECs. This dedifferentiation is accompanied by signatures of proliferation, adhesion remodeling, and endothelial-to-mesenchymal transition. While these changes present challenges for maintaining depot-specific identity in culture, they also provide a framework to better interpret experimental outcomes and to investigate EC plasticity. Taken together, our study delivers a novel isolation and culture protocol for adipose ECs, defines BAT-EC markers, and demonstrates how culture conditions reshape their identity. These insights build the foundation for future research of AT vasculature.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Endothelial Cells ; Brown Adipose Tissue ; Cell Isolation ; Culture ; Heterogeneity ; Plasticity ; White Adipose Tissue; Mesenchymal Transition; Vascular Endothelium; Fat; Heterogeneity; Health; Muscle; Roles; Beige; Rgc32; Gene
ISSN (print) / ISBN
2212-8778
e-ISSN
2212-8778
Journal
Molecular Metabolism
Quellenangaben
Volume: 107,
Article Number: 102349
Publisher
Elsevier
Publishing Place
Amsterdam
Reviewing status
Peer reviewed
Institute(s)
Institute of Diabetes and Cancer (IDC)
Grants
Deutsche Forschungsgemeinschaft (DFG, German Research foundation)