WAT-to-BAT communication facilitates the sustained activation of BAT thermogenesis during cold exposure

  • Cell Discov. 2026 May 26;12(1):37. doi: 10.1038/s41421-026-00891-8.
Jieyuan Xue  #  1  2  3 ,  Ding Chen  #  2 ,  Chenfeng Wang  #  3 ,  Jue Wang  #  4 ,  Jiayu Zhou  3 ,  Wenyan Li  2 ,  Junxi Qian  2 ,  Yuanji Huang  2 ,  Liang Fang  5 ,  Hongyong Song  6 ,  Ben He  7  8 ,  Xu-Yun Zhao  9  10
Affiliations
  • 1. Ruijin Hospital Lu Wan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2. Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3. Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 4. Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5. Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 6. Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 7. Department of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 8. Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China. [email protected].
  • 9. Ruijin Hospital Lu Wan Branch, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • 10. Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 42191682 DOI: 10.1038/s41421-026-00891-8
Abstract

The activation of brown adipose tissue (BAT) for thermogenesis represents a crucial physiological mechanism that helps maintain body temperature during cold exposure. Nevertheless, the exact mechanisms underlying the sustained activation of BAT under cold conditions remain incompletely understood. In this study, we reveal that soluble ST2 (sST2) mediates a white adipose tissue (WAT)-to-BAT endocrine mechanism that is essential for the continuous activation of BAT during cold exposure. Specific depletion of sST2 blocks alternative thermogenesis following BAT denervation and renders mice sensitive to cold during prolonged cold exposure. Mechanistically, sST2 is induced and secreted from epididymal white adipose tissue (eWAT) upon the activation of Creb1, which is driven by β1 and β2 Adrenergic Receptor signaling. Secreted sST2 directly binds to the β3 Adrenergic Receptor in BAT and, in synergy with norepinephrine, induces BAT thermogenesis independent of IL33. Additionally, supplementation with sST2 promotes beige fat formation. Therefore, our study illustrates a novel mechanism through which the adipokine sST2 derived from eWAT mediates sustained BAT activation during cold exposure through the integration of neural and humoral signals. More importantly, sST2 exerts a synergistic effect on BAT activation when combined with β3-adrenergic receptor agonists.

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