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Brown adipose tissue secretes OLFM4 to coordinate sensory and sympathetic innervation via Schwann cells

Author

Listed:
  • Mingqiang Lai

    (Southern Medical University
    Hangzhou Normal University)

  • Wu Zhou

    (Southern Medical University)

  • Wenchong Zou

    (Hangzhou Normal University)

  • Lianlian Qiu

    (Southern Medical University)

  • Zhaoyu Liang

    (Southern Medical University)

  • Wanyi Chen

    (Southern Medical University)

  • Yiqing Wang

    (Southern Medical University)

  • Bin Guo

    (Southern Medical University)

  • Chaoran Zhao

    (Southern Medical University)

  • Sheng Zhang

    (Southern Medical University)

  • Pinglin Lai

    (The Third Affiliated Hospital of Southern Medical University)

  • Le Hu

    (Southern Medical University)

  • Xiaolin Liu

    (Southern Medical University)

  • Yu Jiang

    (School of Medicine)

  • Yinghua Chen

    (Southern Medical University)

  • Min-jun Huang

    (the Third Affiliated Hospital of Southern Medical University)

  • Xiaochun Bai

    (Southern Medical University
    Southern Medical University)

  • Zhipeng Zou

    (Southern Medical University)

Abstract

Non-shivering thermogenesis of brown adipose tissue (BAT) is tightly controlled by neural innervation. However, the underlying mechanism remains unclear. Here, we reveal that BAT regulates its own thermoadaptive innervation by crosstalk with Schwann cells (SCs). Loss of Olfm4 (encoding Olfactomedin-4), a risk gene in human obesity, causes BAT dysfunction and reduces whole-body thermogenesis, predisposing to obesity in mice. Mechanistically, BAT-derived OLFM4 traps Noggin, an endogenous inhibitor of BMPs, liberating BMP7-BMPR1B signaling to promote SC differentiation. Conversely, Olfm4 loss reduced BMP7 signaling in mature SCs, leading to MEK/ERK-dependent dedifferentiation and dysfunction, ultimately impairing both sensory and sympathetic innervation. Thermoneutrality exposure reduces Olfm4 expression in BAT, resulting in a similar phenotype. MEK/ERK inhibition, ERK1 depletion, or cold exposure reverses this SC dedifferentiation, enhancing resistance to obesity. These findings suggest that this neurotrophic BAT-SC crosstalk controls thermoadaptive BAT innervation. Reactivating OLFM4 signaling may be a promising therapeutic strategy for obesity and related metabolic diseases.

Suggested Citation

  • Mingqiang Lai & Wu Zhou & Wenchong Zou & Lianlian Qiu & Zhaoyu Liang & Wanyi Chen & Yiqing Wang & Bin Guo & Chaoran Zhao & Sheng Zhang & Pinglin Lai & Le Hu & Xiaolin Liu & Yu Jiang & Yinghua Chen & M, 2025. "Brown adipose tissue secretes OLFM4 to coordinate sensory and sympathetic innervation via Schwann cells," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60474-1
    DOI: 10.1038/s41467-025-60474-1
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