GEO series

Paracrine stimulation of brown adipose tissue vascularization by adipocyte O-GlcNAc signaling

GSE308294 Mus musculus Expression profiling by high throughput sequencing 8 samples Submitted 2025/12/20 Platform GPL24247

Summary

Brown adipose tissue (BAT) is extensively vascularized, which is essential for its physiological activities. The molecular mechanism that underpins BAT vascularization, however, remains poorly understood. This study presents evidence that acute cold exposure induces an elevation in total protein O-linked β-N-acetylglucosamine modification (O-GlcNAcylation) in BAT. Ablation of O-GlcNAc transferase in brown adipocytes drastically impairs BAT vascularization. Mechanistic studies demonstrate that O-GlcNAcylation of specificity protein 1 (SP1) in brown adipocytes enhances its transcriptional activity towards kielin/chordin-like protein (Kcp). Secreted KCP subsequently promotes BAT angiogenesis by paracrine activation of BMP signaling. Furthermore, boosting O-GlcNAc signaling with glucosamine supplementation effectively augments BAT vascularization and thermogenesis. These findings thus uncover a previously unrecognized role of adipocyte O-GlcNAc signaling in the metabolism-driven regulation of BAT vascularization and function.

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Also filed as BioProject PRJNA1330147 and SRA study SRP621041. Searching any of these in the dataset finder brings you back here.

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