2. Academic Validation
  3. Paracrine stimulation of brown adipose tissue vascularization by adipocyte O-GlcNAc signaling

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

  • Cell Rep. 2025 Dec 23;44(12):116678. doi: 10.1016/j.celrep.2025.116678.
Luwen Li 1,  Liwei Dong 1,  Yaping Shan 1,  Jintang Xie 2,  Ting Song 1,  Sai Zhang 1,  Yun Kong 1,  Shiqi Zhang 1,  Chengwei Gu 1,  Die Hu 3,  Weijia Wang 3,  Yunfan Yang 4
Affiliations

Affiliations

  • 1 Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
  • 2 Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
  • 3 State Key Laboratory of Medicinal Chemical Biology, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin 300071, China.
  • 4 Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China. Electronic address: [email protected].
PMID: 41385373 DOI: 10.1016/j.celrep.2025.116678
Abstract

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 in brown adipocytes enhances its transcriptional activity toward kielin/chordin-like protein (Kcp). Secreted KCP subsequently promotes BAT angiogenesis by paracrine activation of bone morphogenetic protein 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.

Keywords

BMP signaling; CP: metabolism; KCP; O-GlcNAc; brown adipose tissue; vascular system.

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